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259 publications mentioning hsa-mir-26b (showing top 100)

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-26b. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 590
Our data indicated that ectopic overexpression of SMAD1 increases Twist1 expression and when the downregulation of endogenous overexpression of SMAD1 by upregulation of miR-26b-5p expression occurred, Twist1 expression was obviously upregulated (Figure 8A). [score:20]
Third, SMAD1 expression is significantly upregulated in HCC tissues, and this up-regulation is strongly correlated with the down-regulation of miR-26b-5p. [score:12]
Interestingly, E-cadherin mRNA expression was up-regulated by 0.9-fold and 1.9-fold whereas vimentin was down-regulated by 31.8% and 23.7% in HepG2 and MHCC97L cells, respectively, following the upregulation of miR-26b- 5p. [score:12]
Therefore, over -expression of miR-26b-5p inhibits the expression of SMAD1 in HCC cells and high SMAD1 expression correlates with poor prognosis of HCC disease. [score:11]
These findings indicate that miR-26b-5p may negatively regulate the expression of SMAD1 by directly targeting its 3′-UTR and SMAD1 was indeed a direct downstream target of miR-26b-5p. [score:10]
In comparison, protein expression, not mRNA expression of SMAD1 was significantly increased in HepG2-miR-26b-5p -inhibitor and PLC-miR-26b-5p -inhibitor cells (Figure 5B). [score:9]
As Twist1 directly binds to promoter regions of MIR-26B (Figure 1B) to downregulate miR-26b-5p expression, and SMAD1 has been identified as the target for miR-26b-5p, miR-26b-5p may be an important part in this loop. [score:9]
Nevertheless, down-regulation of miR-26b-5p or up-regulation of SMAD1 could enhance Slug expression. [score:9]
This indicates that ectopic overexpression of SMAD1 does not increase BMP4 expression and the restoration of SMAD1-mut rescued the miR-26b-5p -suppressed BMP4 expression. [score:9]
Dual-luciferase reporter analysis showed that expression of miR-26b-5p significantly inhibited the activity of luciferase that carried wildtype but not mutant 3′-UTR of SMAD1 (Figure 5A and 5C), indicating that miR-26b-5p may suppress gene expression through its binding sequence at 3′-UTR of SMAD1. [score:9]
The results of both overexpression miR-26b-5p and ectopically rescuing expression of SMAD1-mut in Bel7402 showed that the overexpression of SMAD1-mut (Figure S2C) rescued miR-26b-5p -mediated decrease of BMP4 expression. [score:9]
When miR-26b-5p is upregulated, the expression levels of SMAD1 are down-regulated accordingly, and the promotion of the EMT process is relieved. [score:9]
Here, we demonstrated that there is an important regulatory axis present in certain situations, such as tumor initiation and metastasis, involving high levels of Twist1 binding to miR-26b-5p to downregulate miR-26b-5p expression, resulting in less SMAD1 suppression, inactivation of BMP4/Smad1 signaling, and the promotion of EMT, ultimately contributing to tumor progression in HCC. [score:9]
The overexpression of miR-26b-5p inhibited EMT, migratory and invasive abilities, and adhesion by inactivating the BMP4/Smad1 signaling pathway through the downregulation of SMAD1. [score:8]
Expression of miR-26b-5p is inversely correlated with Twist1 expression in HCC tissues and its downregulation is associated with patient poor prognosis. [score:8]
Additionally, the levels of E-cadherin and vimentin in the different groups indicated that miR-26b-5p could inhibit the SMAD1 -induced EMT program by downregulating SMAD1 expression (Figure 7B). [score:8]
Over -expression of miR-26b-5p inactivated the bone morphogenetic protein 4 (BMP4)/Smad1 pathway by upregulating SMAD1 in HCC cells and suppressing EMT, tumor migration and invasion. [score:8]
Stable cell lines over -expressing and down -regulating miR-26b-5p were established and were tentatively designated Bel7402-miR-26b-5p or SMMC-miR-26b- 5p, HepG2-miR-26b-5p -inhibitor or PLC-miR-26b-5p -inhibitor. [score:8]
As expected, down-regulation of miR-26b-5p or up-regulation of SMAD1 promoted the EMT phenotype. [score:7]
[23] The human pre-miR-26b-5p gene expression plasmid, miR-26b-5p gene expression inhibitor plasmid and the respective empty vector plasmids were purchased from GeneCopoeia (US). [score:7]
These results indicate that miR-26b-5p directly bind to SMAD1 and down-regulates its expression in HCC. [score:7]
Re -expression of SMAD1 partially abrogated miR-26b-5p -mediated EMT suppressive effects and metastasis suppression. [score:7]
To evaluate whether the over -expression of miR-26b-5p leading to the downregulation of SMAD1 may inactivate the BMP4 pathway, the expression of BMP4 in the different groups was studied. [score:6]
The induction of EMT observed with p-SMAD1-mut in Bel7402-miR-26b-5p cells was associated with the downregulation of E-cadherin and the increased expression of vimentin (Figure 6A and 6B). [score:6]
SMAD1 is identified as the functional downstream target of miR-26b-5p and is upregulated in HCC samples. [score:6]
However, BMP4 expression in the miR-26b-5p -upregulated group was lower than that in the control group. [score:6]
Taken together, miR-26b-5p primarily inhibits BMP4/Smad1 signaling by down -regulating SMAD1 expression, thus demonstrating its indispensable role. [score:6]
In this study, we found that Twist1 -induced EMT was associated with the downregulation of the miR-26b-5p based on miRNA expression profiles and ChIP-seq technology. [score:6]
Moreover, the results obtained from HCC patients were consistent with previous observations that the expression of miR-26b-5p was significantly downregulated in HCC tissues (Figure 1C). [score:6]
al. noted that miR-26b inhibited EMT and acts as tumor suppressor by negatively regulating USP9X in HCC [33]. [score:6]
Over -expression of miR-26b-5p inactivates the BMP4/Smad1 pathway to regulate EMT and metastasis by targeting SMAD1 in HCC cells. [score:6]
In our study, due to miR-26b-5p up or downregulation, Twist1 expression demonstrated no significant change between the treatment group and control group (Figure S4). [score:6]
It was observed that expression of miR-26b-5p suppressed cell adhesion by 49% and 70%, respectively, in Bel7402 and SMMC7721 cells. [score:5]
Potential target genes of miR-26b-5p were first predicted using databases, including TargetScan, PicTar, and miRanda (Table S4). [score:5]
The analysis of miR-26b-5p predicted targets was performed using TargetScan, PicTar, the miRanda algorithms and the complementary DNA (cDNA) microarray results for hepatocellular carcinoma in our previous study. [score:5]
Among these miRNAs, the expression of miR-26b-5p was significantly (P = 0.00733) downregulated in the HepG2-Twist1 cell line compared with the HepG2-vector cell line. [score:5]
HepG2 and PLC cells possess an epithelial phenotype, but following the silencing of miR-26b-5p in HepG2-miR-26b-5p -inhibitor or PLC-miR-26b-5p -inhibitor cells, striking morphological changes consistent with the induction of EMT were observed (Figure S3A). [score:5]
However, miR-26b-5p -inhibitor -transfected HepG2 cells all produced tumors by 10 days after injection, whereas miR-26b-5p -inhibitor-control transfectants produced tumors (mean sizes of 666 to 676 mm [3] by the end of observation) in all mice (Figure 4C) 9 to 11 days after inoculation. [score:5]
Bel7402 and SMMC7721 with P-miR-26b-5p or P-miR-control, and HepG2 and PLC with P-miR-26b-5p -inhibitor or P-miR -inhibitor-control. [score:5]
al. have observed that miR-26b inhibited cell migration and invasion through targeting EphA2 [32]. [score:5]
The 293T cells were transiently cotransfected with P-miR-26b-5p, P-miR-control, P-miR-26b-5p -inhibitor, P-miR -inhibitor-control, pGluc/SEAP-SMAD1–3′UTR-wt, pGluc/SEAP-SMAD1–3′UTR-mt, and pGluc/SEAP-vector. [score:5]
Interestingly, HepG2-miR-26b-5p -inhibitor and PLC-miR-26b-5p -inhibitor cells generated 2~3-fold more and larger colonies than the corresponding control cells, while Bel7402-miR-26b- 5p and SMMC-miR-26b-5p cells demonstrated opposite results (Figure 4B). [score:5]
Moreover, introduction of miR-26b-5p in Bel7402 and SMMC diminished the expression of SMAD1 protein, not the expression of SMAD1 mRNA. [score:5]
First, miR-26b-5p overexpression significantly decreases the expression of SMAD1 at the protein level in HCC cells. [score:5]
Figure 4Stable over -expression of miR-26b-5p suppresses adhesive and colony formation abilities in vitro and tumorigenicity in vivo(A, B) Effects of miR-26b-5p on cell adhesion and colony formation of cancer cell lines. [score:5]
These data indicated that over -expression of miR-26b-5p in HCC with mesenchymal phenotypes inhibited EMT, thus impairing migration and invasion abilities. [score:5]
Stable over -expression of miR-26b-5p suppresses adhesion and colony formation in vitro and tumorigenicity in vivo. [score:5]
The downregulation of miR-26b-5p was associated with the EMT phenotype: expression of miR-26b-5p was lower in mesenchymal phenotypic cells (Bel7402, H7402, HCCLM3 and SMMC7721) compared to cell lines cells with a basal epithelial phenotype (MHCC97L, HepG2, HuH7 and PLC). [score:5]
Stable over -expression of miR-26b-5p suppresses adhesive and colony formation abilities in vitro and tumorigenicity in vivo. [score:5]
All together, our data imply that BMP4/Smad1 signaling can be inhibited through SMAD1 repression by miR-26b-5p, thus suppressing EMT, tumor invasion and metastasis. [score:5]
Using the average expression value obtained for miR-26b-5p from the 23 samples studied as the cut-off point for Kaplan-Meier plots, it was demonstrated that lower miR-26b-5p expression was significantly associated with early metastasis of HCC (Figure 1E). [score:5]
Consistent with these above results, the restoration of SMAD1 inhibited the miR-26b-5p -suppressed migration, invasion, colony formation and cell adhesion (Figure 6C and 6D). [score:5]
The expression of miR-26b-5p and BMP4 were highly inversely correlated (P = 0.01, r = −0.524) and there is a significant positive correlation between SMAD1 expression levels and BMP4 mRNA levels (P = 0.029, r = 0.455) (Figure 8C). [score:5]
First, due to increased miR-26b-5p or the overexpression of SMAD1, or the co-overexpression of miR-26b-5p and SMAD1, a switch in cellular shape between spindle- and fibroblast-like morphologies and the cobblestone-like appearance of epithelial cells was observed (Figure S3B). [score:5]
The reversion of EMT in the Bel7402-miR-26b-5p and SMMC-miR-26b-5p cells was also associated with elevated expression of E-cadherin and the reduced expression of vimentin (Figure 2C and 2D). [score:5]
If SMAD1 indeed acts as a functional target of miR-26b-5p, reintroduction of SMAD1 into miR-26b-5p -expressing cells should be able to antagonize the effects of miR-26b-5p. [score:5]
Pearson correlation analysis showed that miR-26b-5p expression was inversely correlated with Twist1 expression in the clinical samples (Figure 1D). [score:5]
Stable over -expression of miR-26b-5p suppresses adhesion and colony formation in vitro and tumorigenicity in vivoEMT program induction follows a well-coordinated process that includes several steps. [score:5]
Thus, the miR-26 family, in part, has similar function, and is consistently down-regulated in a wide range of malignant tumors, including HCC. [score:4]
As expected, downregulation of BMP4 mRNA and protein levels was observed in the miR-26b-5p/negative control (lane 4), SMAD1-wt/miR-26b-5p (lane 5), and miR-26b-5p/SMAD1-wt (lane 6) groups (Figures 8A, 9). [score:4]
miR-26 regulates numerous target genes simultaneously and its role is completely different in certain tumors. [score:4]
Furthermore, downregulation of miR-26b-5p in a panel of liver cancer cells and HCC patients was associated with a more prominent EMT phenotype and poorer prognosis. [score:4]
To elucidate the molecular mechanisms by which miR-26b-5p regulates EMT in HCC, we employed several computational algorithms [10] to identify the potential functional targets of miR-26b-5p. [score:4]
The data indicate that down-regulation of miR-26b-5p may be responsible for the increased levels of SMAD1 in human HCC tissues, which in turn promotes invasion and metastasis of HCC. [score:4]
Figure 3(A, B) Transwell migration and invasion assays with the Bel7402-miR-26b-5p and SMMC-miR-26b-5p cells (A) and HepG2-miR-26b-5p -inhibitor and PLC-miR-26b-5p -inhibitor cells (B). [score:4]
Our data clearly indicate that miR-26b-5p directly represses invasion and tumor metastasis by inhibiting SMAD1. [score:4]
miR-26b-5p is downregulated in HCC tissues and cell lines and is associated with tumor short-term recurrence and metastasis. [score:4]
The upper panel shows that miR-26b-5p is significantly downregulated in HepG2-vector and HepG2-Twist1 human HCC cell lines. [score:4]
The results indicated that stable overexpression of miR-26b-5p significantly alleviated the migration and invasion abilities of the Bel7402 and SMMC cells in vitro (Figure 3A). [score:3]
The low expression of miR-26 is closely related with short overall survival of HCC patients [33– 37]. [score:3]
The data indicated that the levels of EphA2, Wnt5α and SIP1 were not significantly changed in different groups; the expression of β-catenin, Snail, and Slug, was highest in SMAD1-wt/miR-control group, was lowest in miR-26b-5p/negative control group, and in miR-26b-5p/SMAD1-wt group, fell in between (Figures 8A, 9). [score:3]
Furthermore, a significant increase in cell migration and invasion was observed following transfection of p-miR-26b-5p -inhibitor into HepG2 and PLC cells (Figure 3B). [score:3]
The expression of miR-26b-5p and SMAD1 were highly inversely correlated (P = 0.035, r = −0.442) (Figure 5E). [score:3]
Re -expression of SMAD1 in Bel7402-miR-26b-5p cells, as confirmed by qRT-PCR analysis (Figure S2A), induced a dramatic morphological change in the Bel7402-miR-26b-5p cells (Figure S2B), implicating EMT. [score:3]
These results phenocopied those observed with reduced miR-26b-5p expression. [score:3]
However, the low expression of miR-26b has been found in glioma cells, and its level is inversely correlated with the grade of glioma [30]. [score:3]
Accordingly, the tumorigenic ability of HCC is suppressed by miR-26b-5p in vivo. [score:3]
Figure 6(A) qRT-PCR analysis of the expression of the epithelial protein E-cadherin and the mesenchymal protein vimentin in SMAD1 -transfected Bel7402-miR-26b-5p cells. [score:3]
Inhibition of miR-26b-5p enhanced cell adhesion by 0.86- and 1.14-fold, respectively, in HepG2 and PLC (Figure 4A). [score:3]
SMAD1 is identified as a downstream target of miR-26b-5p. [score:3]
As miR-26b-5p is a Twist1-related miRNA, the expression of Twist1 was detected in the same HCC cell lines by qRT-PCR and Western blot. [score:3]
Among them, SMAD1 was chosen for further experimental validation, not only because it was identified as a target of miR-26b-5p by all three databases, but also due to its well-known importance in both tumor metastasis and EMT. [score:3]
Figure 8(A) qRT-PCR analysis of the expression of BMP4, SMAD1, Snail and Twist1 in SMAD1, miR-26b-5p transfected HepG2 and 97L cells as in Figure 7B. [score:3]
Taken together, these findings show that SMAD1 reintroduction could partially rescue miR-26b-5p -mediated EMT, cell migration and invasion suppression in HCC cells, suggesting that SMAD1 is a functional mediator of miR-26b-5p in HCC cells. [score:3]
Moreover, in the microarray analysis, Slug was excluded from miR-26b-5p potential targets. [score:3]
A previous study also indicated that SMAD1 participates in the EMT process [22], and the morphologies of the Bel7402 and HepG2 cells changed after the alteration of miR-26b-5p or SMAD1 expression (Figure S3). [score:3]
Figure 2(A) Expression of miR-26b-5p was studied in a panel of liver cancer cell lines by qRT-PCR. [score:3]
Representative results for cell adhesion (A) and colony formation (B) of miR-26b-5p -transfected Bel7402 and SMMC7721 cells and miR-26b-5p -inhibitor -transfected HepG2 and PLC cells. [score:3]
Our clinical data suggested that miR-26b-5p expression was markedly decreased in HCC tissues. [score:3]
The average expression value obtained for miR-26b-5p from the 23 samples studied by qRT-PCR was chosen as the cut-off point for survival analysis using the Kaplan-Meier method. [score:3]
The expression of miR-26b-5p in these cells was confirmed by qRT-PCR (Figure S1A and S1B). [score:3]
This growth -inhibitory role of miR-26b-5p may result from decreased proliferation. [score:3]
These results indicate that the introduction of miR-26b-5p significantly inhibited tumorigenicity in a nude mouse xenograft mo del. [score:3]
The results of qRT-PCR and functional assays fell in between when both miR-26b-5p and SMAD1 were upregulated. [score:3]
All data indicate that SMAD1 is involved in miR-26b-5p -suppressed EMT process. [score:3]
Collectively, these findings indicate that miR-26b-5p inhibits both adhesion, colony formation in vitro and tumorigenicity in vivo. [score:3]
Compared to P-miR-control transfected cells, upregulation of miR-26b-5p was associated with the observed dramatic morphological changes in the Bel7402-miR-26b-5p and SMMC-miR-26b-5p cells from an elongated fibroblastic phenotype to an epithelial cobblestone phenotype, which is consistent with the changes associated with mesenchymal-to-epithelial transition (MET) (Figure S3A). [score:3]
In other words, SMAD1 can increase, whereas miR-26b-5p can suppress, HCC cell migration and invasion by the EMT process. [score:3]
In vivo, 5 × 10 [6] SMMC7721 and 1 × 10 [7] HepG2 cells (stably transfected with P-miR-26b-5p, P-miR-26b-5p -inhibitor, and their control vectors) were suspended for each mouse. [score:3]
HCC cells with weakened miR-26b-5p or enhanced SMAD1 expression acquire a high adhesive ability. [score:3]
SMAD1 has been identified as the putative target for miR-26b-5p using several different programs and experimental validation. [score:3]
Re -expression of SMAD1 partially rescued miR-26b-5p -mediated EMT, cell migration and invasion abilities in Bel7402-miR-26b-5p cells. [score:3]
Figure 9Western blot analysis of the expression of EphA2, BMP4, SMAD1, SIP1, TGFβ1, Wnt5α and β-catenin, Snail, and Slug in SMAD1 or miR-26b-5p transfected HepG2 and 97L cells as in Figure 7B (lane 1: control, lane 2: miR-control/negative control, lane 3: SMAD1-wt/miR-control, lane 4: miR-26b-5p/negative control, lane 5: SMAD1-wt/miR-26b-5p, and lane 6: miR-26b-5p/SMAD1-wt). [score:3]
These data indicate a growth -inhibitory role for miR-26b-5p in vitro. [score:3]
The data suggest that the expression of the miR-26b-5p may be associated with EMT in HCC. [score:3]
Therefore, we evaluated Bel7402-miR-26b-5p and SMMC-miR-26b-5p cells, HepG2-miR-26b-5p -inhibitor, and PLC-miR-26b-5p -inhibitor cells for their adhesion abilities. [score:3]
Twist1 could directly bind to the promoter region of MIR-26B (Figure 1B). [score:2]
These data suggested that miR-26b-5p and SMAD1 influenced the migratory and invasive behaviors of HCC cells by regulating the EMT process. [score:2]
In addition, ChIP-seq analysis indicated that Twist1 could directly bind to the promoter region of miR-26b- 5p and the results were validated by ChIP-qRT-PCR (Figure 1B). [score:2]
In summary, we found that miR-26b-5p deregulation correlates with Twist1 -induced EMT. [score:2]
Thus, miR-26b-5p, a Twist1 directly-related miRNA, exerts a steady and exclusive role in the EMT program. [score:2]
MiR-26b-5p inactivates the BMP4/Smad1 pathway and exerts its functions by targeting SMAD1. [score:2]
In this study, using microarrays and ChIP-seq technology to analyze Twist1 directly binding to miRNAs, miR-26b-5p drew our attention. [score:2]
This suggests that miR-26b-5p may play an important role in regulating the adhesive traits of HCC cells by reversing EMT. [score:2]
This result indirectly shows that lower miR-26b-5p levels were associated with higher Twist1 levels. [score:2]
All of the above observations indicate that low levels of miR-26b-5p correlates with Twist1 -induced EMT. [score:1]
The mature miRNA of miR-26a-1 and miR-26a-2 possesses the same sequence, with the exception of two different nucleotides in mature miR-26b. [score:1]
miR-26b-5p is associated with the EMT phenotype in HCC cells. [score:1]
Therefore, the corresponding functional experiments were performed to explore the possible biological significance of miR-26b-5p in EMT. [score:1]
We speculated that miR-26b-5p and SMAD1 correlate with the EMT process in HCC. [score:1]
The results were consistent with our hypothesis that miR-26b-5p impairs these abilities in vitro. [score:1]
miR-26b-5p alleviates migration and invasion abilities of epithelial HCC cells. [score:1]
miR-26b-5p significantly weakened the cell-matrix adhesion both in Bel7402 and SMMC7721 cells. [score:1]
The miR-26 family is composed of miR-26a-1, miR-26a-2 and miR-26b located on chromosomes 3, 12 and 2, respectively. [score:1]
In these two cell lines, we reconfirmed that miR-26b-5p and SMAD1 affected EMT, cell migration, invasion, and adhesion. [score:1]
To test this hypothesis, Bel7402-miR-26b-5p cells were transfected with plasmids carrying mutant-type SMAD1 (p-SMAD1-mut), to avoid the influence of the miRNA, into Bel7402-miR-26b-5p cells. [score:1]
Second, a Dual Luciferase Reporter Assay showed that miR-26b-5p could directly bind to the 3′-UTR of the SMAD1 mRNA. [score:1]
We further explored the pathway by which miR-26b-5p and SMAD1 exert their functions in HCC. [score:1]
Based on xenograft mouse mo dels, tumors derived from miR-26b-5p transfectants are obviously smaller than those of the control group. [score:1]
miR-26b-5p is associated with the EMT phenotype and impairs migratory and invasive abilities in human HCC cell lines. [score:1]
miR-26b-5p is one member of the mature miR-26b family. [score:1]
Fourth, restoration of SMAD1 antagonizes the function of miR-26b-5p. [score:1]
Bar graphs show fold enrichment of Twist1 binding of MIR-26B Transcription Start Site (TSS) region. [score:1]
In our research, SMAD1 was significantly associated with the early recurrence and metastasis of HCC (Figure 5F) and enhanced cell invasion, migration and cell adhesion, which was the inverse of the functions of miR-26b-5p in HCC cells. [score:1]
MiR-26b-5p and SMAD1 affect HCC cell migration and invasion by way of regulation of EMT in HepG2 and MHCC97L cells. [score:1]
The seed sequence of miR-26b-5p (middle) matches the 3′-UTR of SMAD1 (top). [score:1]
Figure 5(A) Sequence alignment of human miR-26b-5p with the 3′-UTR of SMAD1. [score:1]
In (B), (C) and (D), HepG2 and MHCC97L cells were cotransfected with control (lane 1), miR-control/negative control (lane 2), SMAD1-wt/miR-control (lane 3), miR-26b-5p/negative control (lane 4), SMAD1-wt/miR-26b-5p (lane 5), and miR-26b-5p/SMAD1-wt (lane 6). [score:1]
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2
[+] score: 337
Ectopically expressed miR-26b inhibits GC cell invasion and metastasis through direct targeting and negative regulation of KPNA2, and its frequent downregulation is suggested to be part of the mechanism underlying metastasis and progression. [score:12]
The results collectively indicate that miR-26b downregulates KPNA2 expression by directly targeting its 3′UTR. [score:9]
Simultaneous downregulation of KPNA2 and c-Jun proteins was observed in miR-26b -overexpressing cells, suggesting a critical axis of miR-26b -targeted KPNA2/c-jun for GC metastasis and vice versa (Figure 5B, left). [score:8]
To explore the molecular mechanisms underlying the role of miR-26b in GC, TargetScan, a miRBase algorithm, was used and combined with differentially expressed proteins of the GC database from our laboratory isobaric tags for relative and absolute quantification (iTRAQ) (data not shown) to identify the putative protein coding gene targets of miR-26b, particularly those with oncogenic functions (Figure S3A). [score:7]
Another study reported that miR-26b acts as a tumor suppressor in glioma and directly regulates EphA2 expression [39]. [score:7]
We used TargetScan, a miRBase algorithm, combined with differentially expressed proteins from the GC database as well as isobaric tags for relative and absolute quantification (iTRAQ) datasets from our laboratory to identify putative protein- coding gene targets of miR-26b. [score:7]
In summary, our results show that miR-26b, an important metastatic suppressor miRNA, is downregulated in relation to lymph node metastasis progression in GC. [score:6]
Downregulation of KPNA2 is inversely correlated with miR-26b expression in. [score:6]
Additionally, miR-26b was shown to downregulate c-Myc and Cyclin D1 expression [35]. [score:6]
Re -expression of KPNA2 in a miR-26b -overexpressing line or its knockdown in a miR-26b -depleted line was established (Figure S4). [score:6]
analysis revealed 5.87 and 4.43-fold downregulation of miR-26b in CagA-transformed AGS/AZ521 cells (Figure 5C), respectively, indicating that miR-26b is suppressed by CagA. [score:6]
In a previous study [6], differential miRNA expression profile data revealed downregulation of miR-26b in relative to paired normal tissues. [score:6]
Accumulating evidence has shown that miR-26b is downregulated in GC, implying a tumor suppressor role. [score:6]
Downregulation of miR-26b is inversely correlated with KPNA2 expression through CagA and c-jun. [score:6]
MiR-26b overexpression led to significant inhibition in cell migration and invasion, which was partially rescued upon re -expression of KPNA2 (Figure 4A). [score:6]
Three novel miR-26b targets were identified (TNKS1BP1, CPSF7, COL12A1), and the expression of each in cancer stroma shown to be significantly associated with breast cancer recurrence [38]. [score:5]
Zhang et al. [7] reported that miR-26b inhibits adipogenic differentiation via suppressing HMGA1 in the ERK1/2 or JNK MAPK and adipogenesis pathways. [score:5]
Since miR-26b expression was negatively correlated with pathologic features (TNM stage), it is reasonable to hypothesize that loss of miR-26b expression promotes GC metastasis. [score:5]
Previous studies have reported that miR-26b has anti-metastasis (PTEN, EphA2, LARP1, CTGF, PFKFB3, Smad1, TNKS1BP1, CPSF7, COL12A1, Nampt, COX-2 pathway targets), anti-proliferative (CDK8, PTGS2, pRb, CHD1, KPNA2, PTEN-AKT pathway targets), anti-survival (Nampt), anti-epithelial-mesenchymal transition (USP9X), pro-chemosensitivity (NF-κB signaling, TAK1 and TAB3), glycolytic metabolism (PFKFB3) and anti-apoptosis (Smad4, SLC7A11) functions [7, 26– 39]. [score:5]
MiR-26b inhibits GC cell invasion in vitro and metastasis in vivoSince clinicopathological data indicate that miR-26b is closely associated with GC metastasis, we postulated that miR-26b overexpression in GC cells should impede their invasive ability. [score:5]
Notably, c-myc, p53 and E2F1 levels in cell lines stably expressing miR-26b remained unchanged on a western blot (data not shown), while c-jun was significantly suppressed by miR-26b. [score:5]
Therefore, overexpression of miR-26b or suppression of KPNA2 may have therapeutic potential in GC patients with metastasis. [score:5]
Immunoblots of KPNA2 gene expression after (B) miR-26b overexpression or (C) depletion in GC clones. [score:5]
Overexpression and suppression of miR-26b were confirmed using (Figure S1). [score:5]
KPNA2 was further identified as a direct target of miR-26b. [score:4]
To further ascertain whether KPNA2 is a direct target of miR-26b, the 3′UTR and its corresponding mutant counterparts were fused to the pMIR-REPORT Luciferase vector. [score:4]
Duan and co-workers found that downregulation of miR-26b in osteosarcoma elevates the levels of CTGF and Smad1, facilitating metastasis in osteosarcoma (os) [27]. [score:4]
The prognostic significance of miR-26b downregulation in GC was additionally determined via survival analysis. [score:4]
Data from the current study revealed that downregulation of miR-26b enhances GC cell migration and invasion in vitro and metastasis in vivo. [score:4]
We observed significant downregulation of miR-26b (1.46-fold) in from 75/106 cases (p = 0.0318, Mann-Whitney U test), consistent with miRNA profiling data (Figure 1B). [score:4]
Li et al. [45] reported roles of miR-26b in hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion, and confirmed that EphA2 is a direct target. [score:4]
Figure 1(A) The miR-26b level was downregulated in 67.9% (72 of 106) of GC tumors (T), relative to paired normal tissues (N). [score:4]
Downregulation of miR-26b modulates chemoresistance and migration through association with PTEN in non-small cell lung cancer cells and human carcinoma tissues [36]. [score:4]
Downregulation of miR-26b in clinical is correlated with advanced clinical stage and poor prognosis. [score:4]
To establish the mechanisms underlying suppression of miR-26b in GC, we explored the potential regulatory factors of miR-26b. [score:4]
In terms of the underlying mechanism, our experiments showed that CagA of Hp stimulates miR-26b downregulation, although further studies are essential to clarify any potential additional factors involved. [score:4]
Conversely, the KPNA2 level was increased 1.57- and 2.63-fold in AGS and AZ-521 cells depleted of miR-26b, respectively (Figure 3C), confirming regulation of KPNA2 expression by miR-26b in GC. [score:4]
Considering the definition of downregulation as T/N ratio < 0.5-fold, miR-26b was decreased in 67.92%, relative to paired normal tissues. [score:4]
MiR-26b is downregulated in various tumor types [19– 25], suggesting an important role in tumorigenesis and tumor progression. [score:3]
The group of Zhu showed that miR-221 and miR-26b enhance mesenchymal stem cell (MSC) migration towards hepatocyte growth factor (HGF) through activation of PI3K/Akt signaling and targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN) in vitro [26]. [score:3]
Moreover, miR-26b and histological type, a pathological parameter, have independent prognostic value for 5-year cumulative survival, supporting a potential role of metastasis-suppressing miR-26b as a novel prognostic biomarker. [score:3]
Figure 4(A) GC clones stably overexpressing miR-26b were transfected with KPNA2 or control plasmid. [score:3]
Figure 1D illustrates the cumulative survival curves of lower and higher expression groups of miR-26b using the median value (= 0.7) as the cut-off. [score:3]
In addition, western blot analysis revealed that the KPNA2 level is decreased by 0.71- and 0.65-fold in AGS and AZ-521 cells overexpressing miR-26b, respectively (Figure 3B). [score:3]
KPNA2 is involved in miR-26b -mediated suppression of cell migration and invasion. [score:3]
Histological analysis of lungs of mice confirmed inhibition of lung metastasis nodules by miR-26b. [score:3]
The average lung colony formation index was decreased 7.33-fold (p < 0.01, Mann-Whitney U test, Figure 2B) in miR-26b -overexpressing cells and increased 9.08-fold (p < 0.01, Mann-Whitney U test, Figure 2D) in miR-26b -depleted cells. [score:3]
Our findings collectively indicate that low miR-26b expression is correlated with advanced tumor stage and lymph node metastasis. [score:3]
Notably, reporter activities of wild-type 3′ UTR, but not mutant 3′UTR, were suppressed by miR-26b. [score:3]
Notably, miR-26b suppressed KPNA2, both at the mRNA and protein level. [score:3]
The number of cells invading the Matrigel to the lower chamber were determined after (A) miR-26b overexpression in AGS and AZ-521 cell lines. [score:3]
In the current study, we sought to clarify the potential role and related target genes of miR-26b in GC progression and metastasis. [score:3]
An inverse association between KPNA2 protein or mRNA and miR-26b expression was observed in clinical specimens (n = 71; r = − 0.67, p < 0.001 or n = 54; r = − 0.27, p < 0.05, Pearson correlation, Figure 5A). [score:3]
Clinicopathological data indicate that lower expression of miR-26b is associated with GC progression. [score:3]
The mean fold change in miR-26b expression in was 1.364–fold (range, 0.028-15.589) greater, relative to that in paired normal tissues (Figure 1A). [score:3]
Patterns of miR-26b expression displayed a stepwise decrease upon GC progression from the early (I and II) to late (III and IV) stages (p < 0.001, Mann-Whitney U test, Figure 1C). [score:3]
Images of miR-26b -overexpressing and -depleted AGS and AZ-521 cell lines are depicted in Figure S1. [score:3]
To establish the relationship between miR-26b expression and tumor progression, were classified into four subgroups according to clinical stage. [score:3]
To further explore the role of miR-26b in tumor metastasis in vivo, SCID mice were transplanted with stable miR-26b -overexpressing or -depleted AGS cells through the lateral tail vein. [score:3]
Augmentation of miR-26b signaling or function presents a potential therapeutic strategy for inhibition of GC metastasis (Figure 5D). [score:3]
Our data strongly indicate a metastasis suppressor role of miR-26b in GC. [score:3]
Reduced miR-26b expression promoted breast fibroblast migration and invasion. [score:3]
We assessed miR-26b and KPNA2 mRNA expression patterns as described earlier in the same patient groups [6]. [score:3]
Expression of miR-26b in tumor tissues was not associated with age, gender and liver metastasis. [score:3]
Therefore, we attempted to determine the factors accounting for lower expression of miR-26b. [score:3]
Since clinicopathological data indicate that miR-26b is closely associated with GC metastasis, we postulated that miR-26b overexpression in GC cells should impede their invasive ability. [score:3]
To examine the association between miR-26b and invasiveness of GC cell lines, miR-26b -overexpressing and -depleted stable AGS and AZ-521 sublines were established. [score:3]
Clinicopathological correlations of miR-26b expressions and 5-year survival rate in 106 GC patients. [score:3]
Conversely, the migration and invasion abilities of AGS were partially suppressed by shKPNA2 in miR-26b -depleted line (Figure 4B). [score:3]
Establishing a miR-26b-overexpression cell line. [score:3]
The effects of aberrant expression of miR-26b on cell migration and invasion activities were assayed using the Transwell method. [score:2]
The primer sequences for miR-26b binding sites of 11 putative target genes are provided (Supplementary Table S1). [score:2]
Alterations in KPNA2 expression influence miR-26b -mediated migration and invasion Migration and invasion assays using stable AGS and AZ-521 cells. [score:2]
MiR-26b was more significantly downregulated in T3 and T4 groups where the serosal surface of the gastric wall was invaded by cancer, compared to T1 and T2 groups where no invasion was evident (p = 0.001), as well as in relation to higher lymph node status (p < 0.001), lymph node metastasis (p < 0.001), and distant metastasis (p < 0.001). [score:2]
MiR-26b inhibits GC cell invasion in vitro and metastasis in vivo. [score:2]
MiR-26b targets KPNA2. [score:2]
Notably, miR-26b overexpressing AGS and AZ-521 cells exhibited significantly lower migration rates (5.33- and 5.08-fold, Figure S2A) and invasive abilities (3.61- and 4.55- fold, p < 0.001, Mann-Whitney U test, Figure 2A), compared to the respective control cell lines. [score:2]
Figure 2Two days after infection (Lenti-miLacZ/Lenti-miR26b or miRZip-control/miRZip-26b virus), blasticidin (8 μg/ml) or puromycin (4 μg/ml) was added, and cells selected for two weeks. [score:1]
Figure 5The relationship between miR-26b and KPNA2 protein levels was assessed using (A) and IHC analyses. [score:1]
Thus, miR-26b may be a useful independent prognostic tumor marker to predict survival and GC metastasis. [score:1]
The effect of miR-26b on c-jun was further examined in the two cell lines. [score:1]
Interestingly, miR-26b levels were closely correlated with location (p = 0.002), gross type (p < 0.001), histological type (p = 0.003), depth of invasion (p < 0.001), and serosal invasion (p < 0.001). [score:1]
Further research is warranted to establish the potential of miR-26b as a prognostic and therapeutic agent. [score:1]
To further confirm the association between miR-26b and KPNA2 in GC metastasis, rescue experiments were performed. [score:1]
Conversely, miR-26b -depleted cells exhibited markedly higher migration (11.8- and 1.6-fold, p < 0.001, Mann-Whitney U test, Figure S2B) and invasion rates (2.73- and 2.06-fold, p < 0.001, Mann-Whitney U test, Figure 2C), relative to control cell lines. [score:1]
MiR-26b regulates cell invasion. [score:1]
The role of miR-26b in GC progression remains to be established. [score:1]
Establishing a miR-26b -depleted cell line. [score:1]
To further confirm the decrease in miR-26b in GC, was performed using 106 paired GC and normal tissues. [score:1]
The means of T and N for miR-26b were −1.88 and −2.51, respectively. [score:1]
Among these, KPNA2 activity was significantly altered by miR-26b (Figure S3B and S3C). [score:1]
Clinicopathological correlations of miR-26b in. [score:1]
The relationships between miR-26b expression patterns and clinicopathological parameters of GC are summarized in Table 1. The characteristics of the study cases are listed (n = 106). [score:1]
Two days after infection (Lenti-miLacZ/Lenti-miR26b or miRZip-control/miRZip-26b virus), blasticidin (8 μg/ml) or puromycin (4 μg/ml) was added, and cells selected for two weeks. [score:1]
Histological type (p = 0.039, hazards ratio (HR) = 2.263, 95% confidence interval (CI) = 1.042−4.914) and miR-26b (p = 0.045, HR = 2.473, 95% CI = 1.02−5.996) emerged as significant independent prognostic biomarkers for GC in a stepwise forward-conditional multivariate regression mo del. [score:1]
Tan and colleagues identified a novel estrogen/MYC/miR-26 axis that mediates estrogen-stimulated breast cancer cell proliferation via CHD1, GREB1 and KPNA2 [8, 9]. [score:1]
The relationship between miR-26b and KPNA2 protein levels was assessed using (A) and IHC analyses. [score:1]
Multivariate analysis (Cox regression) was performed to determine the independent prognostic potential of miR-26b for GC in relation to the significant clinicopathological parameters in univariate analysis. [score:1]
In the present study, we identified miR-26b as a novel anti-metastatic miRNA in GC significantly associated with clinically advanced stages and lymph node metastasis. [score:1]
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[+] score: 292
Our studies indicate that EphA2 is a novel target gene of miR-26b, and the direct interaction between miR-26b and EphA2 mRNA is supported by several lines of evidence: (1) the 3′UTR of both human and murine EphA2 mRNAs contain a putative binding site (the MRE) for miR-26b with significant seed match; (2) miR-26b suppresses the activity of a luciferase reporter fused with the 3′UTR of EphA2 mRNA in an MRE dependent manner; (3) miR-26b represses the endogenous expression of human/murine EphA2 at both the mRNA and protein level; (4) A previous study has shown that EphA2 gene knockdown by siRNAs resulted in failure of VM formation [29]. [score:9]
Moreover, the results predicted by TargetScan 5.1, miRBase Target and PicTar showed that there was a specific target site of miR-26b on 3′UTR of EphA2 (Fig. 4C) and miR-26b was one of the conserved miRNAs targeting EphA2 in both human and murine (Fig. 4D). [score:9]
The results showed that in normal brain tissues, miR-26b exhibited a relative high level expression, whereas the expression of miR-26b was significantly (p<0.01) down-regulated in glioma samples (WHO I, WHO II, WHO III and WHO IV). [score:8]
This study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. [score:7]
The relative expression of miR-26b was expressed as the ratio of the expression level of U6. [score:7]
However, we did find that over -expression of EphA2 fully rescued from the effects of miR-26b when a EphA2 expression vector lacking the 3′UTR (pCMV6-XL6-EphA2) was delivered into the miR-26b over-expressed U251 and U6 cells (Fig. 7 VI and VIII). [score:7]
EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3′UTR region of EphA2 mRNA. [score:7]
These results indicate that miR-26b is a regulator of Eph2A in glioma cells, and that the miRNA can down-regulate the expression of EphA2 at the protein level. [score:7]
The expression of miR-26b was also down-regulated in the three tested glioma cell lines, U251, U87 MG and C6 (Fig. 1). [score:6]
These results suggested that EphA2 plays a key role in the VM formation, and miR-26b affects the VM formation by down-regulation of EphA2 expression in glioma cells. [score:6]
However, when we transfected these cells with EphA2 expression vector without the 3′UTR regain, the VM destroyed by over -expression of miR-26b were fully restored. [score:5]
The inhibition induced by miR-26b in glioma cells is partly dependent on the expression of EphA2. [score:5]
We found that ectopic expression of miR-26b in U251 and C6 glioma cells resulted in diminished proliferation, migration and invasion activity, accompanied by a low level expression of EhpA2. [score:5]
Ectopic expression of miR-26b significantly suppressed the luciferase activity in HEK-293 cells co -transfected with miR-26b duplex (26b-DP) and Luc+miR-26b MRE, which contained the miR-26b response element (MRE) region in the 3′UTR of human EphA2 (Fig. 5B). [score:5]
In conclusion, this study demonstrates that miR-26b plays a key role in the malignancy of glioma cells by directly regulating EphA2 expression, which affects cell proliferation, migration and invasion. [score:5]
These results provide solid evidence that miR-26b suppresses glioma cell proliferation, migration and invasion activity in a manner dependent on EphA2 expression level. [score:5]
Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. [score:5]
In order to determine the relationship between miR-26b expression and glioma grades, the expression of miR-26b in normal brain tissues, glioma tumors and glioma cell lines was analyzed by real-time stem-loop RT-PCR. [score:5]
Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2. [score:5]
We examined the inhibitory effect of miR-26b on glioma cells at different time points and found that the maximum inhibition was at the 48 h (Fig. 2B). [score:5]
Ectopic expression of miR-26b inhibits glioma cell proliferation in vitro. [score:5]
We then tried to find the target genes of miR-26b using the online miRNA target prediction programs miRanda (http://www. [score:5]
As shown in Fig. 2A, over -expression of miR-26b resulted in the growth inhibition of both U251 human glioma cells and C6 rat glioma cells. [score:5]
The results suggest that over -expression of miR-26b inhibits the ability of invasion and migration of glioma cells. [score:5]
The VM formation in U251 (VI) and C6 (VIII) cells was assessed using an inverted microscope after growth for another 24 h. In the present report we detected the miR-26b expression level in human glioma samples and found that the decreased expression level of miR-26b was negatively correlated with the increased malignancy of glioma. [score:5]
However, further study is needed to determine if EphA2 activity is affected by miR-26b in other cancers with high EphA2 expression, like breast cancer, colon cancer, and prostate cancer; and whether miR-26b-EphA2 dysregulation represents a new mechanism for cellular transformation. [score:4]
Similar results were found in our present study, when miR-26b was over-expressed in U251 and C6 cells, the VM process was impaired, suggesting that miR-26b affects VM formation of glioma cells by down -regulating EphA2. [score:4]
To study the regulation of endogenous EphA2 by miR-26b, 26b-DP was transfected into U251 and C6 cells, both of which express high levels of EphA2. [score:4]
Therefore, we transfected the miR-26b duplex (26b-DP) into glioma cells to determine if down-regulation of EphA2 could affect the VM formation. [score:4]
However, the role of miR-26b in glioma development has not been well documented and little is known about its target genes. [score:4]
In order to further confirm the function of miR-26b as an EphA2 regulator, we next studied the effect of miR-26b in U87 MG glioma cells expressing only low levels of endogenetic EphA 2 [27] (Fig. 4B). [score:4]
We further demonstated that the function of EphA2 is regulated by miR-26b; transfection of miR-26b duplex into U251 and C6 cells inhibited their ability to form VM networks. [score:4]
In this study, the expression of miR-26b in glioma cells and the tissues from glioma patients with certain grades was studied by real-time PCR analysis. [score:3]
Additionally, the effect of abnormal expression of miR-26b on tumor grade needs to be addressed. [score:3]
Indeed, we found that expression of EphA2 was significantly enhanced with the advance of glioma grade(p<0.01), accompanying the decrease of miR-26b (Fig. 4A). [score:3]
A mutation in the seed region of miR-26b MRE of EphA2 3′ UTR was made using the Quick change sit-Directed mutagenesis kit to construct the Luc+MRE mutated 3′UTR vector. [score:3]
To quantitate the expression level of mature miR-26b (MIMAT0000083), the isolated RNA was reverse transcribed and amplified by a two-step quantitative RT-PCR method using the Hairpin-it TM miRNAs qPCR Quantitation Kit (Genepharma, Shanghai, China) according to the manufacturer's protocol. [score:3]
Therefore, we assumed that the decreased expression of miR-26b resulted in the high level of EphA2. [score:3]
Low level expression of miR-26b has been found in glioma cells. [score:3]
The expression of miR-26b in tissues of glioma patients has not been well documented. [score:3]
In contrast, suppression of luciferase activity was almost abolished when the miR-26b MRE was deleted from the 3′UTR of EphA2 (Fig. 5B). [score:3]
0016264.g006 Figure 6(A) Effect of miR-26b over -expression on U87 MG cell proliferation. [score:3]
The expression of miR-26b in glioma samples and U251, U87 MG and C6 cells. [score:3]
The expression of EphA2 protein was reduced ∼70% in C6 cells transfected with miR-26b (Fig. 5C and D). [score:3]
VM formation was also affected by ectopic expression of miR-26b. [score:3]
Effect of miR-26b over -expression on glioma cell migration and invasion. [score:3]
Similarly, the activity of luciferase in the cells co -transfected with miR-26b and the construct Luc+wt EPhA2 3′UTR, which contains the entire 3′UTR region of human EphA2, was suppressed by 60∼70% (P<0.01) (Fig. 5B). [score:3]
Ectopic expression of miR-26b in U251 cells reduced the level of EphA2 protein by ∼60% (p<0.01) (Fig. 5C and D). [score:3]
Total RNA was isolated from the glioma tissues and glioma cells of U251, U87 MG and C6 and real-time PCR was performed to analyze the expression of miR-26b as described in. [score:3]
Recent study confirmed that the expression of miR-26b was changed in several human cancer cell lines including glioma cells, [12]. [score:3]
EphA2 is a predicted target of miR-26b. [score:3]
The relative expression level of mature miR-26b from each sample was determined using the 2(−Delta Delta C(T) Method [42]. [score:3]
Over -expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. [score:3]
A mutation in the seed region of miR-26b MRE of the EphA2 3′ UTR was made using the Quick change sit-Directed mutagenesis kit (Stratagene, CA) according to the manufacturer's instructions. [score:3]
These results suggest that miR-26b plays a key role in the proliferation of some glioma cells, and might function as a tumor suppressor in glioma cell lines. [score:3]
However, the growth inhibition induced by miR-26b was abolished when an antisense of miR-26b (26b-AS) was introduced into the cells (Fig. 2A). [score:3]
Approximately 100 targets of miR-26b were predicted from these programs. [score:3]
The expression of miR-26b becomes lower with increasing grades of glioma. [score:3]
of miR-26b duplex decreased the aggressive feature of glioma cells, suggesting that miR-26b plays a critical role in glioma development, and it may act as an anti-tumor factor in glioma cells. [score:2]
These data indicate that the predicted MRE is critical for the direct and specific binding of miR-26b to EphA2 mRNA. [score:2]
Our study provides evidence that miR-26b acts as an anti-oncogene in glioma cells and is an important negative regulator of the EphA2 gene. [score:2]
Here we found that miR-26b is a negative regulator of EphA2 in VM formation. [score:2]
Compared to U251 and C6 which expressed high levels of EphA2 (Fig. 4A and B), the cell proliferation reduced by miR-26b were not significant (p>0.05) in the U87 MG cells (Fig. 6A). [score:2]
This study helps us to better understand of the function of miR-26b and its regulation of EphA2 in glioma cells. [score:2]
The regulation of miR-26b on EphA2 was confirmed by the experiments of luciferase analysis, Western blotting, and Vasculogenic mimicry (VM) network formation. [score:2]
Additionally, we further confirmed that miR-26b is an important regulator of EphA2, and there was an interaction between miR-26b and EphA2 in glioma cells. [score:2]
26b-DP was transfected into U251 or C6 cells, and the cell proliferation inhibition rates were evaluated by MTT assay at 12, 24, 36, 48 and 72 h. The inhibitory rates of cells were the percentage of the ratio of cells proliferation transfected with miR-26b to that transfected with NC-DP. [score:2]
These results suggest that miR-26b is likely to be an important regulator of EphA2. [score:2]
The level of miR-26b was inversely correlated with the grade of glioma. [score:1]
Proliferation, migration, and invasion were analyzed to confirm the effects of miR-26b in glioma cells. [score:1]
The antisense of two microRNAs, negative antisense of negative control microRNA, cel-miR-67 (NC-AS) and miR-26b antisense (26b-AS) were also provided by Dharmacon. [score:1]
Another construct, Luc+MRE deleted 3′UTR, in which the miR-26b MRE region of EphA2 3′UTR is deleted was also constructed with a similar approach. [score:1]
A binding site for miR-26b was identified in the 3′UTR of EphA2. [score:1]
To construct the luciferase reporter vectors, the predicted miR-26b binding site (miRNA response element, MRE) on the EphA2 3′UTR or the whole 3′UTR of EphA2 were inserted into the XhoI and NotI sites of a psiCheck2 vector (Promega, WI) immediate downstream of the Renilla luciferase gene. [score:1]
Cells were first transfected with miR-26b duplex, negative control RNA duplex, co -transfected with 26b-DP and miR-26b specific antisense oligonucleotides (26b-AS) or negative antisense oligonucleotides (NC-AS). [score:1]
The miR-26b seed sequences and their predicted binding sites in the EphA2 3′UTR are shown underlined. [score:1]
Another microRNA mimics is 26b-DP, which is a duplex of miR-26b. [score:1]
Real-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. [score:1]
miR-26b binds to the 3′UTR of EphA2 mRNAs. [score:1]
U87 MG cells were first transfected with miR-26b duplex, negative control RNA duplex (NC-26DP), co -transfected with 26b-DP and miR-26b specific antisense oligonucleotides (26b-AS), or negative antisense oligonucleotides (NC-AS). [score:1]
The sense and antisense sequences of the MRE were synthesized, annealed, and ligated into the psiCheck2 vector to construct a miR-26b MRE luciferase reporter, Luc+miR-26bMRE. [score:1]
We next determined the effect of miR-26b on the proliferation of glioma cells. [score:1]
VM formation was also abolished in glioma cells transfected with the miR-26b duplex. [score:1]
miR-26b is one of the miRNAs involving in the response to hypoxia, a well documented tumor microenvironment factor [11]. [score:1]
Effects of miR-26b on proliferation, migration and invasion in U87 MG cells. [score:1]
The predicted MRE or the whole EphA2 3′UTR was inserted into a psiCheck2 vector immediately downstream of the Renilla luciferase gene to construct the luciferase reporter vectors, Luc+miR-26b MRE and Luc+wt EphA2 3′UTR, respectively. [score:1]
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[+] score: 222
Other miRNAs from this paper: hsa-mir-199a-1, hsa-mir-199a-2
Since overexpression of miR-26b suppressed the proliferation of MDA-MB-231 breast cancer cells, and given that PTGS2 is a direct target of miR-26b, we hypothesized that the inhibitory effect of miR-26b on breast cancer cell viability might be achieved via targeting PTGS2. [score:12]
In this study, we report that miR-26b expression is significantly decreased in human breast cancer, and its overexpression inhibits the proliferation of MDA-MB-231 cells by targeting PTGS2. [score:9]
Previous studies demonstrated that overexpression of miR-26b in DFOM -treated CNE cells inhibited proliferation via degradation of PTGS2 mRNA and suppression of PTGS2 protein translation [8]. [score:9]
The overexpression of miR-26b inhibits cellular growth by targeting PTGS2, suggesting its use as a potential therapeutic target for breast cancer. [score:9]
s using a reporter carrying a putative miR-26b target site in the 3' untranslated region of PTGS2 revealed that miR-26b directly targets PTGS2. [score:8]
Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells, possibly via regulation of its downstream target, EphA2 [23]. [score:8]
These results demonstrate that downregulation of PTGS2 expression by miR-26b contributes, at least in part, to the suppression of the growth of breast cancer cells. [score:8]
To confirm targeting of PTGS2 by miR-26b, we integrated a fragment of the PTGS2 3 [′]-UTR containing the target sequence, or a fragment whose target site was mutated, into a luciferase reporter vector. [score:7]
MiR-26b directly downregulates PTGS2 and inhibits breast cancer cell proliferation. [score:6]
Overexpression of miR-26b led to downregulation of PTGS2 at the mRNA and protein level, as assessed by and Western blot. [score:6]
To investigate the downstream targets of miR-26b that may play a role in mediating this growth suppressive effect, we searched for putative targets using the miRanda database. [score:5]
Furthermore, overexpression of miR-26b induces apoptosis in MCF-7 breast cancer cells by targeting SLC7A11 [11]. [score:5]
Overexpression of miR-26b suppressed MDA-MB-231 cell growth. [score:5]
In conclusion, these findings support the hypothesis that decreased expression of PTGS2 by miR-26b accounts for the suppression of cellular proliferation in breast cancer. [score:5]
Furthermore, miR-26b has been shown to directly silence PTGS2 and regulate PTGS2 expression in desferrioxamine (DFOM) -treated carcinoma of nasopharyngeal epithelial (CNE) cells [8]. [score:5]
These results indicate that miR-26b functions as a tumor suppressor, whose dysregulation may be involved in the initiation and development of human breast cancer. [score:5]
Consistent with this study, Xiao-Xiao Liu et al. reported that miR-26b expression is downregulated in MCF7, HCC1937, MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-549 and BT-474 breast cancer cell lines compared with CCD-1095Sk normal breast skin cells [11]. [score:5]
Taken together, these studies indicate that dysregulated expression of miR-26b may affect multiple cancers. [score:4]
Previous studies reported that miR-26b mimics triggered apoptosis of human breast cancer MCF7 cells, and SLC7A11 was identified as a direct target of miR-26b [11]. [score:4]
Figure 3 PTGS2 is a direct target of miR-26b in breast cancer. [score:4]
These data indicate that miR-26b directly interacts with PTGS2 mRNA and represses PTGS2 protein expression. [score:4]
These results indicate that miR-26b is downregulated in human breast cancer specimens and cell lines. [score:4]
MiR-26b expression was significantly downregulated in breast cancer specimens compared with normal tissue. [score:4]
An increasing body of evidence indicates that miR-26b is downregulated in hepatocellular carcinoma [7], nasopharyngeal carcinoma [8], primary squamous cell lung carcinoma [9], squamous cell carcinoma of the tongue [10] and in breast cancer [11]. [score:4]
Figure 1 miR-26b is relatively downregulated in breast cancer. [score:4]
These results suggest that miR-26b directly targets PTGS2 in breast cancer cells. [score:4]
s were conducted to explore the impact of miR-26b overexpression on the proliferation of human MDA-MB-231 breast cancer cells. [score:3]
Figure 2 miR-26b inhibits the proliferation of breast cancer cells. [score:3]
These data indicate that miR-26b may serve as a tumor suppressor gene involved in breast cancer pathogenesis. [score:3]
Suppression of breast cancer proliferation by miR-26b. [score:3]
MiR-26b regulates PTGS2 expression in breast cancer cells. [score:3]
MiR-26b inhibits the proliferation of breast cancer cells via regulation of PTGS2. [score:3]
The aim of this study was to investigate the expression pattern of microRNA-26b (miR-26b) in human breast cancer, and its potential role in disease pathogenesis. [score:3]
Luciferase reporter assays were employed to validate regulation of a putative target of miR-26b. [score:3]
Expression of miR-26b is decreased in human breast cancer. [score:3]
The effect of modulating miR-26b on endogenous levels of this target were subsequently confirmed via and Western blot. [score:3]
Taken together, these results demonstrate that miR-26b inhibits the proliferation of MDA-MB-231 breast cancer cells. [score:3]
Taken together, we demonstrate that miR-26b is downregulated in breast cancer specimens compared with normal tissue. [score:3]
Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-26b in 38 breast cancer specimens and adjacent normal breast tissues. [score:3]
For detection of miR-26b expression, primer design and was performed as previously described [25]. [score:2]
As shown in Figure  3C and 3D, the expression of PTGS2 mRNA and protein was decreased in MDA-MB-231 cells transfected with 100 nM miR-26b mimics compared with the control. [score:2]
Luciferase activity was significantly repressed in cells transfected with the construct harboring the miR-26b target sequence compared with the mutated control vector. [score:2]
This inhibitory effect was significantly enhanced following transfection with 100 nM miR-26b at 48 h (14%), 72 h (29%) and 96 h (28%) (P<0.05) compared with the negative control. [score:2]
The 3 [′] untranslated region (3 [′] UTR) of PTGS2 containing the predicted miR-26b binding site was amplified by PCR in a total volume of 50 μl using the Primer star kit (Takara) in accordance with the manufacturer’s instructions. [score:2]
MiR-26b may act as a tumor suppressor in breast cancer. [score:2]
However, to date, the role of miR-26b in breast cancer tumorigenesis is incompletely understood. [score:1]
Gain- and loss-of-function studies showed that miR-26b and its host genes CTDSP1/2/L cooperate to block G1/S-phase progression by activating pRb protein in hepatocellular carcinoma [24]. [score:1]
We identified a binding site for miR-26b in the 3 [′]-UTR of PTGS2 mRNA. [score:1]
In this study, we performed to investigate the expression pattern of miR-26b in primary human breast cancer. [score:1]
Computational algorithms revealed that the 3 [′]-UTR of PTGS2 contains a binding site for miR-26b. [score:1]
MiR-26b expression was significantly decreased in breast cancer tissues compared with NATs (7.3 fold, P<0.01) (Figure  1). [score:1]
Furthermore, luciferase activity was also decreased following co-transfection of psiCHECK-2/PTGS2 3 [′]-UTR mutant and miR-26b (Figure  3B). [score:1]
The next day, sub-confluent (50-60%) cells were transfected with miR-26b mimics (50 nmol/L and 100 nmol/L) or PTGS2 siRNA (50 nmol/L) (Genepharma, China) using Lipofectamine 2000 (Invitrogen, USA), in accordance with the manufacturer’s instructions. [score:1]
psiCHECK-2/PTGS2 3 [′]-UTR or psiCHECK-2/PTGS-2 3 [′]-UTR mutant reporter plasmids (200 ng) were co -transfected with miR-26b mimics or miR-NC (100 nM) into MDA-MB-231 cells (60% confluence) using Lipofectamine 2000 (Invitrogen), in accordance with the manufacturer’s instructions. [score:1]
The effect of miR-26b transfection on endogenous PTGS2 mRNA and protein expression was subsequently evaluated in MDA-MB-231 cells by and Western blot. [score:1]
Both PTGS2 mRNA and protein levels decreased after transfection of MDA-MB-231 cells with miR-26b, as shown in Figure  3C and 3D. [score:1]
To validate miR-26b binding to this predicted site, we cloned the 3 [′]-UTR of PTGS2 containing the putative miR-26b binding site into a luciferase reporter construct, in addition to a mutated PTGS2 3 [′]-UTR (Figure  3A). [score:1]
As shown in Figure  2, cellular proliferation gradually declined following transfection with miR-26b, in a concentration -dependent manner. [score:1]
In our study, transfection of miR-26b mimics into MDA-MB-231 cells led to a significant decrease in cellular proliferation, indicating that miR-26b represses the growth of breast cancer cells. [score:1]
DMEM medium was replaced with DMEM supplemented with 10% FBS 5 h post-transfection with miR-26b mimics or PTGS2 siRNA. [score:1]
MiR-26b expression was relatively decreased in breast cancer specimens compared with adjacent normal tissues (P<0.01). [score:1]
In glioma, low levels of miR-26b were inversely correlated with tumor grade. [score:1]
These results indicate that miR-26b specifically binds to the 3 [′]-UTR of PTGS2. [score:1]
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5
[+] score: 211
Other miRNAs from this paper: hsa-mir-204, rno-mir-26b, rno-mir-204
To further investigate the therapeutic role of miR-26b in human tissues, we transfected hPASMCs with miR-26b mimics, CTGF or CCND1 specific siRNA, and examined the inhibitory effect of miR-26b on the expression levels of CTGF and CCND1 in hPASMCs, finding that the effect of specific siRNA was similar to that of miR-26b with respect to the inhibition of the expression of the designed target gene, whereas only miR-26b could suppressed the expression of both CTGF and CCND1 (Figure 4). [score:13]
Taken together, we showed that PASMCs from monocrotaline -induced pulmonary artery remo deling are different from the normal controls in their microRNA repertoire, and miR-26b, a microRNA significantly downregulated in pulmonary artery remo deling, contributes to the development of PAH via releasing the inhibition of its two target genes, CTGF and CCND1, both of which have been repeatedly reported to be involved in the pathogenesis of the disease. [score:11]
The discovery of the downregulation of miR-26b in pulmonary artery remo deling, as well as its regulation of its target genes, CTGF and CCND1, may have important implications in our understanding of the molecular mechanisms underlying PAH, and may also lead to the development of new therapeutic interventions in this devastating and life-threatening disease. [score:10]
Considering the reports that the upregulation of CTGF and CCND1 substantially contributes to the development of pulmonary vascular remo deling, as well as the observation that miR-26b significantly suppresses CTGF and CCND1 expression, we next evaluated its effect on monocrotaline -induced pulmonary vascular remo deling, and determined the influence of miR-26b/EXGEN500 complex on the expression of CTGF and CCND1 in parallel with CTGF and CCND1 shRNAs in monocrotaline -treated rats. [score:9]
Figure 4 A. Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the mRNA expression level of CTGF in hPASMCs (p<0.01); B. lower panel: Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the protein expression level of CTGF in hPASMCs, as determined by western blot; upper panel: densitometric analysis of the western blot results underneath (p<0.01); C. Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the mRNA expression level of CCND1 in hPASMCs (p<0.01); D. lower panel: Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the protein expression level of CCND1 in hPASMCs, as determined by western blot; upper panel: densitometric analysis of the western blot results underneath (p<0.01). [score:9]
Furthermore, the most significantly down-regulated miRNAs, miR-26b, was selected for further functional analysis due to its well documented role in regulating human cell proliferation [30, 31], as well as the predicted function to suppress the expression of CTGF and CCND1(www. [score:9]
A. Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the mRNA expression level of CTGF in hPASMCs (p<0.01); B. lower panel: Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the protein expression level of CTGF in hPASMCs, as determined by western blot; upper panel: densitometric analysis of the western blot results underneath (p<0.01); C. Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the mRNA expression level of CCND1 in hPASMCs (p<0.01); D. lower panel: Effect of introduction of anti-CTGF siRNA, anti-CCND1 siRNA, has-miR-26b mimics and control on the protein expression level of CCND1 in hPASMCs, as determined by western blot; upper panel: densitometric analysis of the western blot results underneath (p<0.01). [score:9]
In addition, miR-26b almost completely restored the monocrotaline -induced up-regulation of CTGF and CCND1, while shRNA only partially lowered the expression of its designed target, as shown in Supplementary Figure S2 and S3. [score:8]
To elucidate how miRNAs are involved in PAH pathogenesis, we investigated and compared global miRNA expression profiles in PASMCs isolated from monocrotaline -treated rats and normal control using microarray and selected the most significantly down-regulated miRNAs, miR-26b, for further functional analysis due to its documented role in regulating human cell proliferation [27], as well as the virtual function to suppress the expression of CTGF and CCND1 predicted by online microRNA databases such as www. [score:8]
In this study, we found that overexpression of miR-26b, but not the control, substantially repressed the activity of luciferase fused with 3′-UTR of CTGF and CCND1 respectively, but had minimal effect on the luciferase activity fused with mutated 3′-UTRs, as shown in Figure 1. In addition, we found that relative expression of miR-26b in the rPASMCs isolated from monocrotaline -treated rats was significantly downregulated compared with the control. [score:7]
Figure 2 A. Determination and comparison of expression of rno-miR-26b between rPASMCs harvested from monocrotaline -treated and normal saline -treated rats (p<0.01); B. Determination and comparison of mRNA expression level of CTGF in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, and miR-26b (p<0.01); C. Determination and comparison of mRNA expression level of CCND1 in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, and miR-26b (p<0.01); D. Upper panel: Densitometry analysis of the western blotting results to show the relative protein levels of CCND1 in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, miR-26b; Lower panel: Results of western blot (p<0.01); E. Upper panel: Densitometry analysis of the western blotting results to show the relative protein levels of CTGF in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, miR-26b; Lower panel: Results of western blot (p<0.01). [score:7]
MiR-26b has been shown to be able to suppress the proliferation of human multiple myeloma cells via targeting a number of candidate genes including CTGF [39]; Meanwhile, Yang et al demonstrated in their study about human breast cancer that miR-26b inhibited breast cancer progression through modulating Fra-1 proto-oncogene [27]. [score:7]
In the present study, we found that downregulation of miR-26b was responsible for the upregulation of CTGF and CCND1 in monocrotaline -induced pulmonary artery remo deling, and intratracheal administration of miR-26b could almost completely restore the pulmonary artery remo deling in monocrotaline -treated rats. [score:7]
Site-directed mutagenesis of the miRNAs binding sites in the 3′UTRs was performed using Site-Directed Mutagenesis Kit (SBS Genetech, Beijing, China) and named as mutant 3′UTRs, as shown in Figure 1. rPASMCs grown in a 48-well plate were co -transfected with 400 ng of either individual miR-26b, 40 ng of the firefly luciferase reporter plasmid including the 3′-UTR of the target gene, and 4 ng of pRL-TK, a plasmid expressing rellina luciferase (Promega, Madison, WI, USA). [score:7]
As shown in Figures 2B-2E, the treatment with miR-26b/EXGEN500 complex significantly attenuated both CTGF and CCND1 mRNA/protein expression in rat pulmonary vessels compared with the control, while the two shRNAs specifically downregulated its designed target with minimal effect on the other one. [score:7]
A. Determination and comparison of expression of rno-miR-26b between rPASMCs harvested from monocrotaline -treated and normal saline -treated rats (p<0.01); B. Determination and comparison of mRNA expression level of CTGF in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, and miR-26b (p<0.01); C. Determination and comparison of mRNA expression level of CCND1 in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, and miR-26b (p<0.01); D. Upper panel: Densitometry analysis of the western blotting results to show the relative protein levels of CCND1 in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, miR-26b; Lower panel: Results of western blot (p<0.01); E. Upper panel: Densitometry analysis of the western blotting results to show the relative protein levels of CTGF in rPASMCs harvested from the rats treated with normal saline, monocrotaline+NCshRNA, CTGF shRNA, CCND1 shRNA, miR-26b; Lower panel: Results of western blot (p<0.01). [score:7]
By searching online microRNA databases, we identified both CTGF and CCND2 as potential targets of miR-26b, the most down-regulated one. [score:6]
Treatment with monocrotaline significantly downregulated miR-26b expression in rats. [score:6]
Considering the previous reports that miR-26b inhibited human cell proliferation, and the observation that miR-26b substantially suppressed the expression of CTGF and CCND1, we subsequently evaluated the efficacy of miR-26b in the treatment of monocrotaline -induced pulmonary artery remo deling in parallel with CTGF or CCND1 shRNA, and found miR-26b, CTGF shRNA, or CCND1 shRNA significantly decreased the pulmonary vessel wall thickness (42%, 45%, 20%, of monocrotaline treated, respectively) in monocrotaline -treated rats. [score:5]
Figure 2A showed that relative expression of miR-26b in the rPASMCs isolated from monocrotaline -treated rats was significantly down-regulated to about 20% compared with the control (*P<0.01). [score:5]
In vitro analysis of the inhibitory effect of miR-26b on the expression of CTGF and CCND1 in comparison with CTGF or CCND1 specific siRNA in hPASMCs. [score:5]
We reasoned that miR-26b may exert protective effect via inhibiting both CTGF and CCND1, or possibly involved some other PAH-related genes which are not necessarily a complete match, and therefore not predictable by the online target predicting tool. [score:5]
Furthermore, we showed in this study that the miR-26b also significantly blocked monocrotaline -induced upregulation of α-SM-actin in rats, and the shRNAs could only partially restored it (Supplementary Figure S4). [score:4]
In this study, a similar delivery efficiency and a better efficacy of miR-26b/EXGEN500 were exhibited in the treatment of same disease, and this may shed a light on the development of therapeutic tool in treat PAH in human. [score:4]
Effect of CTGF siRNA, CCND1 siRNA and miR-26b on the expression of CTGF and CCND1 in rPASMCs. [score:3]
The results demonstrated that even though CTGF or CCND1 shRNA treatment successfully inhibited the pulmonary vascular remo deling induced by monocrotaline, but neither of them could completely restore the pulmonary artery remo deling induced by monocrotaline, while miR-26b could almost completely restore it. [score:3]
We found that overexpression of miR-26b, but not the control mimics, substantially repressed the activity of luciferase fused with wild-type 3′-UTR of CTGF and CCND1, respectively, but had minimal effect on the luciferase activity fused with mutated 3′-UTR of CTGF or CCND1, as shown in Figures 1D, 1E (*P<0.01). [score:3]
Louis, MO, USA) and negative control shRNA (as therapeutic control); Group III: Treated with monocrotaline and CTGF shRNA; Group IV: Treated with monocrotaline and CCND1 shRNA; Group V: Treated with monocrotaline and miR-26b (No difference was identified regarding the observed parameters such as cell proliferation, vascular thickness, the expression of CTGF, CCND1,α-SM actin, or cell cycle progression between the rats treated with or without normal saline, and between the rats treated with monocrotaline and monocrotaline+ NCshRNA (Negative control shRNA), as presented in our previous studies, so we narrowed down the original seven groups to five experimental groups in this study). [score:3]
Figure 1 A. The “seed sequence” in the 3′ UTR of the target gene of rno-miR-26b is highly conserved among the species including, but not limited to, Rno, Has, Ptr, Mml, Oga, Tbe, and Mmu; B. Schematic comparison between rno-miR-26b and the wild-type (upper sequence)/mutated (lower sequence) 3′UTR of CTGF with “seed sequence” highlighted; C. Schematic comparison between rno-miR-26b and the wild-type (upper sequence)/mutated (lower sequence) 3′UTR of CCND1 with “seed sequence” highlighted; D. The relative luciferase activity in the rPASMCs transfected with both wild-type 3′UTR of CTGF and rno-miR-26b is significantly lower than the controls (p<0.01); E. The relative luciferase activity in the rPASMCs transfected with both wild-type 3′UTR of CCND1 and rno-miR-26b is significantly lower than the controls (p<0.01). [score:3]
Furthermore, we validated CTGF and CCND1 as effective targets of miR-26b by using a luciferase reporter system. [score:3]
Effect of MCT, CTGF shRNA, CCND1 shRNA and miR-26b on the expression of CTGF and CCND1 in rPASMCs. [score:3]
These results indicated that treatment with miR-26b substantially induced G1 cell cycle arrest in rPASMCs, and its inhibitory effect was stronger than that of in the groups treated with CTGF or CCND1 shRNA. [score:3]
Flow cytometry analysis of the inhibitory effect of miR-26b on cell cycle progression in comparison with CTGF or CCND1 shRNAs in rPASMCs. [score:3]
Sequence comparison between miR-26b and 3′UTR of CTGF and CCND1. [score:1]
A. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with normal saline; B. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline+NCshRNA; C. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and CTGF shRNA; D. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and CCND1 shRNA; E. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and rno-miR-26b. [score:1]
The results demonstrated that even though CTGF or CCND1 shRNA treatment successfully attenuated the pulmonary vascular remo deling induced by monocrotaline, nevertheless neither of them could completely restore the pulmonary artery remo deling, which can be done by introduction of miR-26b alone. [score:1]
For gene delivery in vivo, plasmid -based CTGF or CCND1 shRNA, miR-26b, or its negative control were mixed with EXGEN500 and 5% glucose (Fermentas Biotechnology Co. [score:1]
Effect of MCT, CTGF shRNA, CCND1 shRNA and miR-26b on the cell cycle status in rPASMCs. [score:1]
Meanwhile, the treatment with CTGF or CCND1 shRNA, and miR-26b significantly decreased the pulmonary vessel wall thickness (42%, 45%, 20% of monocrotaline -treated, respectively) in monocrotaline -treated rats (H&E staining, images not shown). [score:1]
Briefly, the oligonucleotides for CTGF or CCND1 shRNAs, miR-26b or the negative control were synthesized chemically or PCR-amplified, and linked into the pGPU6/GFP vector which contains a mouse U6 RNA polymerase III promoter. [score:1]
Figure 3 A. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with normal saline; B. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline+NCshRNA; C. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and CTGF shRNA; D. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and CCND1 shRNA; E. Flow cytometric determination of cell cycle status in rPASMCs harvested from the rats treated with monocrotaline and rno-miR-26b. [score:1]
Plasmids containing miR-26b, CTGF or CCND1 shRNA, or the control were mixed with EXGEN500/5% Glucose prior to intratracheal administration. [score:1]
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[+] score: 209
qPCR analysis demonstrated that 7/11 NF-κB -dependent genes were downregulated to less than 0.5-fold after transfecting with miR26b*, and 6/11 NF-κB -dependent genes were downregulated to less than 0.5-fold after transfecting with miR562, confirming the inhibition of NF-κB activity. [score:9]
The same notions apply to attempting to down-regulate expression of miR26b* or miR562 in order to down-regulate NF-κB activity in breast cancer cells. [score:9]
It is crucial to understand that regulation of p65 by miRs occurs before the post-translational modifications of p65 and that the post-transcriptional regulation of p65 by miR26b* affects the expression and levels of p65 itself while the post-translational modifications of p65 may affect function and activity of p65. [score:9]
Our data on miR26b* is novel as no miR has been experimentally shown to target Rel A. However, p65 (protein encoded by Rel A) has been shown to induce the expression of some miRs such as hsa-miR-143 that directly targets fibronectin type III domain containing 3B (FNDC3B) that regulates adipocyte differentiation [26]. [score:9]
A decrease in fold-induction of NF-κB-promoter activity after PMA treatment was observed in cells over -expressing either miR26b* or miR562, indicating that miR26b* and miR562 was able to down-regulate NF-κB activity (Fig. 3C), while miRs were overexpressed (Fig. 3D). [score:8]
Functionally, higher expression of both miR26b* and miR562 in MCF7 cells lead to increased endothelial cell tube formation while inhibition of miR26b* and miR562 inhibited tube formation. [score:7]
0114507.g003 Figure 3 (A,B) qPCR expression of NFKB1 after miR26b* and miR562 overexpression in MCF7 and MCF7-V5 cells (overexpressing ANXA1). [score:7]
This data confirm that miR26b* and miR562 directly target and down-regulate RNA and protein levels of Rel A/p65 and NF-κB1/p105, respectively. [score:7]
In primary tumors, non-invasive tumors or low ANXA1 expressing tumors (such as MCF7), ANXA1 may play a tumor suppressive role by keeping NF-κB activity in check via miR26b* regulation. [score:6]
In summary, we have shown that ANXA1 can modulate the expression of miR26b* and miR562, which are able to functionally down-regulate NF-κB activity both at promoter and downstream effector levels, which may lead to higher endothelial cell tube formation and lower wound healing capacity (with respect to miR562). [score:6]
The elucidation of molecular targets of miR26b* and miR562 has shed more light on miR regulation on NF-κB subunit expression. [score:6]
Direct targeting of Rel A and NF-κB1 by miR26b* and miR562 respectively contributes to the understanding of how NF-κB subunits can be regulated post-transcriptionally. [score:5]
miR26b* and miR562 overexpression in MCF7 cells enhances endothelial cell angiogenesis while silencing miR26b* and miR562 inhibits angiogenesis. [score:5]
Our studies have contributed to understanding the ANXA1-NF-κB signaling paradigm further, highlighted the regulation 2 miRNAs by ANXA1, namely miR26b* and miR562 which directly targeted an NF-κB subunit REL-A (p65) and NF-κB1 (p105), respectively. [score:5]
NF-κB activity was inhibited by both miR26b* and miR562, leading to the inhibition of NF-κB dependent genes which are important in wound healing/migration and angiogenesis. [score:5]
It can be postulated that high expression of ANXA1 leads to a lower expression of miR26b* and miR562 which results in increased NF-κB activity. [score:5]
NF-κB1 was inhibited after transfecting MCF-7 cells with miR26b* or miR562, and this inhibition was reversed in MCF7-V5 ANXA1 stably transfected cells (Fig. 3A,B). [score:5]
This data suggest that miR26b* and miR562 expressed in breast cancer cells can regulate tube formation by endothelial cells. [score:4]
We next determined if NF-κB -dependent genes such as MMP1 or MMP9 were also downregulated in MCF-7 cells transfected with miR26b* or miR562 (Fig. 3D,E). [score:4]
miR26b* directly targeted the Rel A subunit at the 3′ UTR. [score:4]
MicroCOSM, a bioinformatics prediction tool, was used to predict putative targets of miR26b* and miR562 which were related to the NF-κB pathway. [score:3]
Both miR26b* and miR562 over -expression in MCF7 cells resulted in an increase in average number of tubes formed (Fig. 6A,C) as well as average length of tubes formed (Fig. 6B,D). [score:3]
miR26b* and miR562 targets REL-A and NFκB1, respectively. [score:3]
Anti-miR26b* and anti-miR562 might prove to be effective angiostatic agents to inhibit tumor angiogenesis, thus curbing further growth and metastasis. [score:3]
Low ANXA1 levels lead to higher levels of miR26b* which result in lower NF-κB activity in primary tumors or low-ANXA1 expressing tumors. [score:3]
miR26b* and miR562 overexpression modulates NF-κB activity. [score:3]
In MCF7 cells where either miR26b* or has-miR562 was inhibited, there was a reduction in the average number of tubes formed (Fig. 6C). [score:3]
RNA levels of Rel A decreased in MCF7 cells when miR26b* was transiently over-expressed in these cells (Fig. 4D). [score:3]
miR26b* was predicted to target Rel A, whose protein product is p65, at the 3′ UTR end of the gene transcript. [score:3]
Conversely, we also show that higher expression of miR26b* and miR562 can result in reduced NF-κB activity. [score:3]
As we have previously shown that ANXA1 can regulate NF-κB activity [7], we next elucidated if miR26b* or miR562 could be regulating NF-κB. [score:3]
To confirm that NF-κB was indeed modulated by the 2 miRs studied, HEK 293T cells transiently expressing either miR26b* or miR562 were transfected with a construct harboring a NF-κB -binding site upstream of a luciferase reporter and stimulated with PMA. [score:3]
Hence, the ANXA1-NF-κB signaling paradigm described previously by Bist et al [7] has gained clarity with miR26b* and miR562 being able to target p65 and p105 respectively. [score:3]
S1 Fig MiR26b* and miR562 overexpression in MCF7 cells does not modulate proliferation. [score:3]
In the 3′ UTR analysis of Rel A, luciferase activity was completely inhibited when miR26b* was co -transfected with the 3′ UTR of Rel A in HEK 293T cells, indicating complete binding of miR26b* to the 3′UTR of Rel A (Fig. 4C). [score:3]
These observations demonstrate that has-miR26b* and has-miR562 target Rel A and NF-κB1 at the 3′ UTR respectively. [score:3]
3′UTR cloning and target analysis of miR26b*/RelA and miR562/NF-κB1. [score:3]
Fig. 2A–C show that miR26b* and miR562 expression are reduced when ANXA1 is high. [score:3]
Lower levels of miR-26b* (Fig. 2E) and miR562 (Fig. 2F) were expressed in MDA-MB231 with no significant change in MCF-7. These data confirm that high levels of ANXA1 correlate with low levels of miR-26b* and miR562. [score:3]
Expression of miR26b* and miR562 in breast cancer cells. [score:3]
miR26b* and miR562 regulate NFκB activity in breast cancer cells. [score:2]
miR26b* and miR562 have been shown to regulate endothelial cell tube formation in MCF7 cells, which relates to angiogenesis. [score:2]
Next, the endothelial cell tube formation assay was performed to assess the effect of miR26b* and miR562 expression in MCF7 cells on endothelial cell tube formation (co-culture). [score:2]
S1 Fig. illustrates that no difference in growth rates were observed when either miR26b* or miR562 were transfected under the conditions studied (S1 Fig. ). [score:1]
No significant difference was noted in wound closure between control and miR26b* cells, indicating that miR26b* did not affect migration in MCF7 cells. [score:1]
MCF7 cells were transfected with empty vector (EV), miR26b* or miR562 and (A) proliferation rates analyzed using crystal violet staining daily (B) or cell cycle analysis performed using propidium iodide staining. [score:1]
0114507.g006 Figure 6 MCF7 cells were transfected with empty vector (EV), miR26b* or miR562 and a co-culture using transwells was performed with HUVEC in matrigel. [score:1]
Subsequently, the precursor forms of hsa-miR26b*(miR26b*) and hsa-miR562 (miR562) were selected and cloned from human blood peripheral monocytes. [score:1]
Similar co-culture experiments were performed with MCF7 cells silenced with control, anti-miR26b* and anti-miR562. [score:1]
miR26b* is located on chromosome 2 at co-ordinates 219267369–219267455 and miR562 is located on the same chromosome 2 at co-ordinates 233037363–233037457 (Fig. 1C). [score:1]
MCF7 cells were transfected with empty vector (EV), miR26b* or miR562 and a co-culture using transwells was performed with HUVEC in matrigel. [score:1]
More significantly, two novel miRs, hsa-miR26b* and hsa-miR562 were characterized and their targets were elucidated and experimentally validated. [score:1]
We have shown that endogenous levels of miR26b* and miR562 are lower in MDA-MB-231 cells where ANXA1 levels are high and NF-κB activity is constitutively active. [score:1]
A partial rescue (64.4±5.9% rescue) of luciferase activity was observed when miR26b* was co -transfected with the mutated Rel A 3′ UTR plasmid, suggesting that more nucleotides in the seed sequence may need to be mutated. [score:1]
miR26b* and miR562 enhance tumor cell induced endothelial cell tube formation. [score:1]
The seed sequences of both has-miR26b* and has-miR562 have 6 nucleotides, out of which 5 are binding nucleotides (Fig. 4A,B). [score:1]
Effects of miR26b* and miR562 on wound healing. [score:1]
To confirm this, cell cycle analysis was performed and once again, no difference in cell cycle progression was observed for both miRNAs, indicating that both miR26* and miR562 do not affect proliferation in MCF7 cells. [score:1]
Interestingly, miR26b* is the passenger strand (3p) produced together with hsa-miR26b. [score:1]
0114507.g002 Figure 2 (A–C) RNA from MCF10A breast epithelial cells, MCF7 and MDA-MB231 breast cancer cells were isolated and expression levels of ANXA1, miR26b* and miR562 were measured. [score:1]
0114507.g005 Figure 5(A) MCF7 cells were transfected with empty vector (EV), miR26b* or miR562 and wound healing was observed at 0 h, 6 h and 24 h. Representative pictures are presented and (B) % wound closure analyzed. [score:1]
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[+] score: 155
Fig. 4Expression of Wnt4, Wnt5ɑ, Ser9-GSK-3β, CyclinD1 and β-catenin, *, the comparison between Mock group and NC group, P < 0.05. a, of Wnt4, Wnt5ɑ, Ser9-GSK-3β, CyclinD1 and β-catenin expression; b, relative expression of Wnt4 and Wnt5ɑ in the 4 experimental groups; c, relative expression of Ser9-GSK-3β andβ-catenin in the 4 groups; d: relative expression of GSK-3β and CyclinD1in the 4 groups (4 groups: Mock, NC, miR-26b mimic and miR-26b inhibitor group). [score:13]
Although the cellular functions of miR-26b remain elusive, miR-26b inhibits NF-κB pathway in HCC cells by suppressing TAK1 and TAB3 expression, and down-regulation of miR-26b suppressed apoptosis in HCC cells [18]. [score:12]
After 24 h of transfection, GFP express was visible and this expression significantly increased after 48 h. Fig. 1 Expression of green fluorescent protein (GFP) in RAFLS at 24 and 48 h post-transfection Figure  2 shows that the expression level of miR-26b in both Mock group and NC group were 1.05 ± 0.05 and 1.04 ± 0.06, respectively (P > 0.05). [score:9]
In our study, miR-26b elevated the expression of β-catenin and CyclinD1 by lowering GSK-3β expression, which in-turn activated Wnt/GSK-3β/β-catenin pathway, inhibited RAFLS apoptosis and led to increased secretion of TNF-α,IL-1β and IL-6. Thus, miR-26b plays a central role in pathways controlling inflammation in reumatoid arthritis. [score:7]
In summary, miR-26b inhibits RASF proliferation and reduces secretion of inflammatory cytokines, including TNF-α,IL-1β and IL-6, via inhibiting Wnt/GSK-3β/β-catenin pathway through regulating GSK-3β level. [score:6]
Jong Hui Suh et al. demonstrated that miR-26a, which has the same core sequence with miR-26b, is indeed a functional gene product and is capable of binding to GSK-3 β and directly regulating its expression [44]. [score:5]
MiR-26b regulates β-catenin and CyclinD1 levels by inhibiting GSK-3β expression, which in-turn alters the Wnt/GSK-3β/β-catenin pathway to lower RAFLS proliferation and elevate cell apoptosis and the secretion of TNF-α,IL-1β and IL-6 cytokines. [score:5]
The experimental set-up consisted of 4 groups: the Mock group, negative control (NC group transfected with miR-26b negative control sequence), miR-26b mimics group (transfected with miR-26b mimics) and the miR-26b inhibitor group (transfected with miR-26b inhibitor). [score:5]
In miR-26b inhibitor group, miR-26b expression level was 0.23 ± 0.04, significantly lower than Mock and NC groups (all P < 0.05). [score:5]
Conversely, the expression level of GSK-3β and CyclinD1 in the miR-26b inhibitor group was higher than the Mock and NC group (P < 0.05). [score:5]
Fig. 2The expression of miR-26b in each transfection group, *, the comparison between Mock group and NC group, P < 0.05 (NC, negative control) Using bioinformatics Target Scan software (http://www. [score:5]
MiR-26b may be useful to down-regulate SF hyperplasia and inhibit synovium inflammation. [score:5]
In the miR-26b mimic group, expression levels of Ser9-GSK-3β and β-catenin were higher than Mock and NC groups (all P < 0.05), while in the miR-26b inhibitor group, their levels were significantly lower (all P < 0.05). [score:5]
Previous studies showed that the miR-26 family, consisting of miR-26a and miR-26b, is down-regulated in several cancers such as hepatocellular carcinoma (HCC), melanoma, nasopharyngeal carcinoma and breast cancer [27– 31]. [score:4]
Conversely, GSK-3β and CyclinD1 expression levels were markedly higher in the miR-26b inhibitor group compared to Mock and NC group (P < 0.05). [score:4]
org), the potential target-genes of miR-26b were analyzed. [score:3]
Fig. 3GSK-3β is the target of miR-26b. [score:3]
In the miR-26b inhibitor group, RAFLS apoptosis was significant lower than the Mock and NC groups (all P < 0.05). [score:3]
In this study, transfection of miR-26b led to a significant increase in total GSK-3β and a decrease in the inhibitory phosphorylation on Ser9-GSK-3β, strongly influencing Wnt/GSK-3β/β-catenin pathway. [score:3]
On the other hand, in the miR-26b inhibitor group, the cytokines levels were higher than in the Mock and NC groups (all P < 0.05). [score:3]
Therefore, we believe that miR-26b is specific to this pathway and has a prominent role in inhibiting RA synovial inflammation. [score:3]
Confirmation of miR-26b expression by real-time quantitative PCR. [score:3]
Confirmation of target-gene of miR-26b by dual-luciferase reporter gene system. [score:3]
In the miR-26b inhibitor group, the proliferation capacity of RAFLS was significant higher than Mock and NC groups (all P < 0.05). [score:3]
Apoptosis rate of RAFLS in miR-26b inhibitor group is lower than Mock and NC group, while the rate in miR-26b mimic group is higher than Mock and NC group; apoptosis rates between Mock and NC group showed no significant differences). [score:3]
Transfection of miR-26b mimics significantly increased the, levels of Ser9-GSK-3β and β-catenin in comparison to Mock and NC groups, while transfection of miR-26b inhibitors showed the opposite effect. [score:3]
Therefore, our results show that miR-26B plays a central role in inhibiting the inflammation associated with rheumatoid arthritis. [score:3]
By contrast, GSK-3β and CyclinD1 expression levels in miR-26b mimic group were lower than the Mock group and NC group (all P < 0.05). [score:3]
In miR-26b mimic group, TNF-α, IL- 1β and IL-6 levels were lower than the Mock and NC groups, while in miR-26b inhibitor group, these cytokine levels were higher than the Mock and NC groups (P < 0.05). [score:3]
GSK-3β and CyclinD1 expression levels were lower in miR-26b mimic group compared to Mock group and negative control (NC) group. [score:2]
a: the comparison between miR-26b and 3′UTR of GSK-3β, the red part is complementary sites (core sequence, also can be regarded as miR-26b is act on the hypothetical gene loci of GSK-3β gene; GSK-3β 3′-UTR is highly conserved between species) b: Dual-luciferase assay for reporter gene analysis; detected in RAFLS cotransfected miR-26b mimics and GSK-3β 3′-UTR Wt/Mu plasmid; miR-26b inhibited activity of luciferase containing Wt 3′-UTR, *P < 0.05, while Mut plasmid activity of luciferase showed no change. [score:2]
In miR-26b mimic group, the RAFLS cell proliferation capacity was significantly lower than the Mock and NC groups (all P < 0.05). [score:1]
Fig. 7 Effects of miR-26b on RAFLS apoptosis (Q1:necrotic cells; Q2:apoptotic cells; Q3:living cells; Q4:early apoptotic cells. [score:1]
The 3′-UTR of GSK-3β was highly conserved between different species and contained the binding site for mir-26b (Fig.   3a). [score:1]
Thus far, the main role of miR-26b was described in cancers. [score:1]
Plasmids (1 μg) carrying the respective miR-26b sequences were mixed separately with serum-free medium and 2.5 μl lipofectamine 2000 and incubated at room temperature for 15 min under serum-free conditions to form transfection complexes. [score:1]
Real-time quantitative polymerase chain reaction (PCR) technique for measurement of miR-26b expression. [score:1]
However, in the miR-26b mimic group, RAFLS apoptosis was markedly higher than observed in the Mock and NC groups (all P < 0.05). [score:1]
However, in the miR-26b mimic group, these cytokine levels were significantly lower than the Mock and NC groups (all P < 0.05). [score:1]
Transfection of miR-26b mimics significantly reduced the cell proliferation of RAFLS, compared to the Mock and NC groups, and miR-26b inhibitors increased the proliferative capacity of RAFLS compared to Mock and NC groups (P < 0.05). [score:1]
Our study revealed that transfection of miR-26b significantly inhibited NF-κB activity, as judged by the sharply decreased levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6. Although the exact mechanism of this effect need to be further investigated, we believe that miR-26b is intimately involved in RA progression and miR-26b based strategies have the potential to be highly effective against synovium inflammation in RA, consistent with earlier observations by Turner-Brannen et al. [50]. [score:1]
It is interesting to note a significant decrease in RASF proliferation after miR-26b transfection. [score:1]
RAFLS were cultured in vitro and transfected with miR-26b mimics (experimental group) and negative sequence (control group). [score:1]
As shown in Fig.   3b, recombinant plasmids containing Wt- miR-26b/GSK-3β and Mut- miR-26b/GSK-3β were constructed and cotransfected with miR-26b mimics. [score:1]
The miR-26b mimic group exhibited higher RAFLS apoptosis rate compared to Mock and NC group and miR-26b inhibitor group showed significantly lower RAFLS apoptosis rate compared to Mock and NC groups (P < 0.05). [score:1]
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[+] score: 127
Second, by simultaneously binding to and inhibiting transcription of the host genes encoding miR-26a and miR-26b, Myc enforces this upregulation by inhibiting post-transcriptional silencing of EZH2 mRNA. [score:8]
Transient transfection of miR-26a and miR-26b mimics into 5 prostate cancer cell lines resulted in suppressed proliferation, indicating that these MYC targets of repression may have tumor-suppressive functions in the context of prostate cancer. [score:7]
Decreased miR-26b expression has been reported in liver, head and neck cancers, and in hormone refractory prostate cancer [46, 50, 51], while its upregulation was reported in bladder cancer [52]. [score:6]
Interestingly, the 3′UTR of EZH2 contains target sites for miR-26a and miR-26b, and EZH2 was shown to be targeted for repression by miR-26a in muscle and lymphoma cells [21, 22], and of miR-26b in HeLa cells [23]. [score:5]
There was also was an induction of CDH1 and ADRB2, known EZH2 target genes, following miR-26a and miR-26b overexpression in LNCaP cells (Fig. S2 B). [score:5]
Myc was previously reported to regulate the expression of miRNAs [17], including miR-26a and miR-26b in P493 lymphoma cells, by direct binding to their host Pol II gene promoters (CTDSPL, CTDSP2, CTDSP1). [score:5]
In summary, we report that Myc can activate EZH2 expression in prostate cancer by 2 distinct mechanisms-via direct transcriptional activation of the EZH2 promoter, as well as via repression of miR-26a and miR-26b, which themselves can repress EZH2. [score:4]
Next, to determine the relevance of miR-26a and miR-26b in clinical prostate cancer, we measured their expression in 18 matched normal and primary prostate cancer specimens (Table S 2) and found both to be downregulated in cancer in most cases (Wilcoxon signed rank test, p=0.0005 for miR-26a, p=0.079 for miR-26b) (Fig. 6 A, Fig. S 3A). [score:4]
Previous work in muscle, lymphoma and HeLa cells have shown that miR-26a and miR-26b can negatively regulate EZH2 expression, and that this occurs via binding to the highly conserved predicted miR-26a/b binding site within the 3′ UTR of EZH2 [21- 23]. [score:4]
MiR-26a and miR-26b Regulate EZH2 Expression in Human and Murine Prostate Cancer Cells. [score:4]
Figure 5(A,B) MiR-26a and miR-26b repress EZH2 protein (A) and mRNA (B) expression. [score:3]
MYC siRNA pools (Dharmacon, L-003282), siCONTROL Non-Targeting siRNA pool #1 (Dharmacon, D-001810), miRIDIAN Mimic hsa-mir-26a (Dharmacon, C-300499), miRIDIAN Mimic hsa-mir-26b (Dharmacon, C-300501) and miRIDIAN microRNA Mimic Negative Control #1 (Dharmacon CN-001000) were transfected at a final concentration of 50nM. [score:3]
The reporter promoters were transfected along with a Renilla control plasmid, and either non -targeting siRNA, MYC siRNA, miR-26a mimics, or miR-26b mimics. [score:3]
Studies carried out in lymphoma cells and hepatocelluar carcinoma cells have shown that Myc represses the expression of a number of miRNAs, including miR-26a and miR-26b [17, 21]. [score:3]
To determine if mir-26a and miR-26b can target EZH2 in prostate cancer cells, we transfected miR-26a and miR-26b mimics into one mouse and four human prostate cancer cell lines. [score:3]
We observed a reduction in EZH2 mRNA levels in all 5 cell lines (p<0.05), and a similar decrease in EZH2 protein following transient overexpression of miR-26a and miR-26b (Fig 5 A, B). [score:3]
As such, Myc may contribute to EZH2 elevation in prostate cancer, by directly activating EZH2 transcription, and by repressing its negative regulators, miR-26a and miR-26b. [score:3]
Thus, whether miR-26a and miR-26b facilitate oncogenesis, or act as a tumor suppressor, may depend on the cellular context. [score:3]
Hence, we hypothesized that Myc may be a key driver of EZH2 overexpression in PIN and prostate cancer lesions via repression of miR-26a and miR-26b. [score:3]
MiR-26a and miR-26b are incorporated into the RISC complex and bind specifically to their complementary site on the 3′ UTR of EZH2, destabilizing EZH2 mRNA and repressing its translation. [score:3]
In the Lo-MYC mouse mo del, there was a significant negative correlation between the expression of EZH2 mRNA and miR-26a (Spearman rank correlation coefficient= −0.8667, p=0.0045), as well as EZH2 mRNA and miR-26b (Spearman rank correlation coefficient= −0.8167, p=0.0108) (Fig. S2 A). [score:3]
There was a significant inverse correlation between the expression of MYC and miR-26a (Spearman rank correlation coefficient= −0.357, p=0.032), while that for MYC and miR-26b did not achieve statistical significance (Fig. 6 B, Fig. S 3B). [score:3]
Myc represses miR-26a and miR-26b expression. [score:3]
Further, miR-26a and miR-26b expression was increased in MYC-CaP cells after MYC depletion (p<0.02 for both) (Fig. 4 D). [score:3]
In general, miR-26b expression was also reduced in the tumors, though this reduction was not as consistent. [score:3]
EZH2 is a reported target of miR-26a in muscle and lymphoma cells [21, 22], and of miR-26b in HeLa cells [23]. [score:3]
To determine if MYC may be directly regulating miR-26a via repression of CTDSPL and CTDSP2, and miR-26b via repression of CTDSP1, we carried out chromatin immunoprecipitation on LNCaP and PC3 cells. [score:3]
EZH2 is a target of miR-26a and miR-26b in prostate cancer. [score:3]
Additionally, we observed decreased miR-26a and miR-26b expression in the Lo-MYC mice, as compared to the wildtype controls. [score:2]
Mature miR-26a and miR-26b expression was measured by Taqman assay (Applied Biosystems) according to manufacturer's instructions, and normalized against U6 expression. [score:2]
Myc Regulates miR-26a and miR-26b in Human and Murine Prostate Cancer Cells. [score:2]
Co-transfection with either miR-26a mimics, miR-26b mimics or Myc siRNA resulted in reduced reporter activity, as compared to transfection with a non -targeting miR (p<0.03) (Fig. 5 C). [score:2]
Concurrently, MYC represses CTDSPL, CTDSP2 and CTDSP1, in which miR-26a and miR-26b are embedded. [score:1]
MiR-26a and miR-26b have been reported to be Myc -repressed in lymphoma cells [17, 21]. [score:1]
Following MYC-depletion, we found a coordinate increase in the mRNA levels of CTDSPL, CTDSP2 and CTDSP1, and both the mature and primary forms of miR-26a and miR-26b in all 4 cell lines (p<0.02 for all) (Fig. 4 A). [score:1]
Additionally, we measured the expression of the mature and primary forms of miR-26b, and CTDSP1, the gene which harbors miR-26b. [score:1]
This suggests that Myc -mediated repression of miR-26a and miR-26b may be an important factor in maintaining the proliferative capacity of prostate cancer cells. [score:1]
Using this construct, there was no significant reduction in reporter activity following co-transfection with miR-26a mimics, miR-26b mimics or Myc siRNA (Fig. 5 C). [score:1]
In prostate cancer cells, we found that both miR-26a and miR-26b repressed both EZH2 mRNA and protein. [score:1]
We also observed significant inverse correlations between miR-26a and EZH2 mRNA (Spearman rank correlation coefficient= −0.516, p=0.0013), and miR-26b and EZH2 mRNA (Spearman rank correlation coefficient= −0.3552, p<0.0392) (Fig. 6 C, Fig. S 3C). [score:1]
Since MYC represses the transcription of CTDSPL, CTDSP2 and CTDSP1, when MYC levels are low, these genes, which harbor miR-26a and miR-26b, are actively transcribed. [score:1]
To verify specific associations between miR-26a and miR-26b and their predicted binding site on the EZH2 3′UTR in prostate cancer cells, we cloned the 3′UTR of EZH2 into a luciferase reporter vector [21]. [score:1]
In LNCaP and PC3 cells, we observed an enrichment of Myc binding at the promoter regions of CTDSPL, CTDSP2 and CTDSP1, genes whose introns harbor the miR-26a and miR-26b primary transcripts. [score:1]
To determine the biological relevance of miR-26a and miR-26b in prostate cancer cells, we assessed the effect of miR-26a and miR-26b transfection on the proliferation of 4 human prostate cancer cell lines and the Myc -driven mouse prostate cancer cell line. [score:1]
By quantitative real-time PCR, we found that Myc represses miR-26a and miR-26b in all prostate cancer cell lines studied. [score:1]
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[+] score: 112
As miRNAs downregulate their targets on a posttranscriptional level, we also analyzed HDAC4, CDK6, and SMAD1 protein expression during osteogenic differentiation (up to day 12) of USSC 86b and in response to ectopic expression of miR-26a, miR-26b, and miR-29b in native USSC86b. [score:10]
Detailed data for all experimental validation studies are presented in Additional file 2. In summary, we identified osteo -inhibitory targets for miR-10a, miR-22, miR-26a, miR-26b, and miR-29b with the highest targeting impact resulting from miR-26a, miR-26b, and miR-29b expression. [score:9]
To clarify the contradictory roles of osteo-promoting SMAD1 and osteo -inhibitory CDK6 and TOB1 as parallel targets of miR-26a and miR-26b, we directly analyzed target protein abundance by quantitative Western blotting (i) during osteogenic differentiation of USSC and (ii) in response to transfection of USSC with miRNA mimics. [score:8]
Functional analyses demonstrated that miR-26a, miR-26b and miR-29b positively modulate osteogenic differentiation of USSC, most likely by downregulating osteo -inhibitory target proteins. [score:8]
Figure  3 summarizes the results of experimental validations from all 22 predicted miRNA-target interactions: CDK6 was targeted by miR-22, miR-26a, miR-26b, and miR-29b; CTNNBIP1 was regulated by miR-10a and miR-29b; SMAD1 and TOB1 were both recognized by miR-26a and miR-26b; and HDAC4 was targeted by miR-29b. [score:8]
miR-26a and miR-26b expression was confirmed in all native USSC lines and both miRNAs were upregulated in differentiated SA8/77 and SA4/101 lines (Additional file 1). [score:6]
We also identified the osteo -inhibitory BMP/SMAD regulator TOB1 [51] as a target of miR-26a and miR-26b. [score:6]
A recent study of miRNA expression signatures asssociated with osteogenic commitment of USSC showed upregulation of similar miRNAs (miR-26b, miR-30b, let-7a, let-7f and miR-181a) as determined in our analysis [62]. [score:6]
Among these inhibitors, CDK6, CTNNBIP1, HDAC4, TGFB3, and TOB1 were experimentally identified as targets of miR-26a, miR-26b, and miR-29b. [score:5]
Our experimental target validations indicate that miR-26a, miR-26b, and miR-29b likely have the strongest impact on osteogenic differentiation of USSC by reducing osteo -inhibitory CDK6 and HDAC4 proteins. [score:5]
miRNA expression profiling followed by target validation indicated that miR-26a, miR-26b, and miR-29b had the highest impact on osteogenic differentiation in our USSC lines. [score:5]
In contrast to osteo-promoting SMAD1, osteo -inhibitory CDK6 protein expression was indeed reduced 48h post transfection with miR-26a, miR-26b, and miR-29b mimics. [score:5]
In summary, we detected a subset of miRNAs, notably miR-26a, miR-26b and miR-29b, which is consistently upregulated during osteogenic differentiation of USSC. [score:4]
CTNNBIP1 was also regulated by miR-10a and CDK6 [45] was targeted by miR-22, miR-26a, miR-26b and miR-29b. [score:4]
miR-26a modulates late osteogenic differentiation of hADSC through SMAD1 targeting [31] and we showed that both, miR-26a and miR-26b regulate SMAD1, this protein is known as a positive mediator of osteogenic differentiation [59]. [score:4]
As with HDAC4, our results confirm that miR-26a, miR-26b, and miR-29b target CDK6. [score:3]
The sheet “deep sequencing” indicates results from deep-sequencing derived expression analysis of miR-26a and miR-26b in native USSC SA5/73, SA8/25, SA8/77, and SA4/101 and osteo-differentiated USSC SA8/77 and SA4/101. [score:3]
Interestingly, miR-26a and miR-26b were also predicted to regulate SMAD1, a positive regulator of osteogenic differentiation [55]. [score:3]
Interestingly, SMAD1 expression remained unchanged at day 9 post DAG induction compared to native USSC 86b (Figure  5E) and was not affected by transfection with miR-26a and miR-26b mimics (Figure  5F). [score:2]
Summarizing results from both CDK6-3 [′]-UTR fragments, significant regulatory miRNA effects were seen for miR-22, miR-26a, miR-26b, and miR-29b, whereas miR-137 had no significant effect. [score:2]
Despite targeting of the SMAD1 3 [′]-UTR by miR-26a and miR-26b in our luciferase assay (Figure  3), SMAD1 protein abundance remained unaltered upon transfection with miR-26a/b mimics (Figure  5F). [score:2]
The strongest effect on osteogenic differentiation was observed by transfecting an equimolar mixture of miR-26a, miR-26b, and miR-29b mimics. [score:1]
Transfection of USSC SA5/73 with miR-26a/miR-26b/miR-29b mimics further increased differentiation (Figure  6A). [score:1]
Here we identified strong interactions between CDK6-2 and miR-26a and miR-26b and moderate interactions with miR-29b. [score:1]
USSC SA5/73 and USSC 86b were each transfected with (i) a small unspecific negative control RNA, (ii) an equimolar batch of miR-26a and miR-26b, (iii) miR-29b, and (iv) an equimolar batch of miR-26a, miR-26b, and miR-29b mimics (SA5/73 only), each followed by DAG induction. [score:1]
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[+] score: 89
For top 10 downregulated microRNAs (hsa-miR-106b-5p, hsa-miR-26b-5p, hsa-miR-494, hsa-miR-425-5p, hsa-miR-363-3p, hsa-miR-15b-5p, hsa-miR-185-5p, hsa-miR-150-5p, hsa-miR-223-3p, hsa-miR-142-5p), we included those have been shown to be deregulated in cancer (having no controversial expression status; some of these microRNAs have been shown to be upregulated in some cancer types, whereas, downregulated in other cancer types), and have either expression data or functional studies in stem cells. [score:15]
Among those significantly differentially expressed miRNAs, five downregulated (miR-26b-5p, miR-200c-3p, miR-203a, miR-223-3p, miR-363-3p) and three upregulated (miR-328, miR-574-3p, miR-1825) miRNAs were selected as a result of detailed literature search for further confirmation with qRT-PCR. [score:9]
MicroRNA profiling of CD133 [+] and CD133 [−] LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133 [+] larynx CSLCs. [score:7]
Given that miR-26b is downregulated in both stem cells and cancer cells, our findings suggest miR-26b as a CSLC specific miRNA, whose deregulation might participate in oncogenic transformation and maintenance of stem cell state in larynx CSLCs and as well as others. [score:5]
Among those, miR-26b (Fig.   2a, b), miR-200c (Fig.   2c, d), miR-203 (Fig.   2e, f), and miR-363-3p (Fig.   2g, h) were found to have significantly reduced expression in CD133 [+] larynx CSLCs, whereas miR-1825 (Fig.   2i, j) were validated to have increased expression in these CD133 enriched LCa cells. [score:5]
Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. [score:5]
Fig. 2 a Relative expression levels of miR-26b in each CD133 [+] and CD133 [−] sample pairs, and (b) mean relative expression levels miR-26b in CD133 [+] cells with respect to CD133 [−] cells. [score:5]
As to the analysis of validated targets of these miRNAs, miRTarBase database analysis revealed that miR-26b, miR-200c, miR-203, and miR-363-3p, and miR-1825 cooperatively target stem cell associated signaling pathways like Wnt, Hedgehog, and Notch (Fig.   4). [score:5]
MiR-26b expression has been found to be downregulated in tongue [58], nasopharyngeal carcinoma [59], and oral cancers [60]. [score:5]
To evaluate their correlation, we used Pearson correlation analysis, which demonstrated that miR-26b, miR-200c, and miR-203 expressions were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively, in CD133 [+] LCa tissue samples (Fig.   3). [score:3]
Exposure to cigarette smoke, as a major risk factor for LCa, was proposed to cause repression of miR-26 family members’ expressions in animal mo dels [61]. [score:3]
Furthermore, miRWalk analysis showed that 3’UTR of several oncogenes were predicted to be targeted by miR-26b (202 out of 348 oncogenes), miR-200c (161 out of 348 oncogenes), miR-203 (216 out of 348 oncogenes), and miR-363-3p (175 out of 348 oncogenes). [score:3]
We, in the present study, showed that CD133 [+] LCa cells possess reduced miR-26b expression. [score:3]
To validate the differential expression of miR-26b, miR-200c, miR-203, miR-223, miR-328, miR-363-3p, 574-3p, and miR-1825, a total of 25 pairs of CD133 [+] and CD133 [−] cell populations collected from 25 tumor samples including those used in microarray experiments were studied. [score:3]
Additionally, miR-26b expression in neural stem cells was found to be induced during their differentiation into neurons in vivo [66]. [score:3]
In addition to miR-200c and miR-203, which have been demonstrated in distinct cancers as having CSLCs specific deregulation pattern, we propose miR-1825, miR-363-3p, and miR-26b as specific miRNAs with potential roles in acquisition and maintenance of stem cell associated features as well as in contributing to tumor initiation, progression, metastasis, chemoresistance, and recurrence. [score:2]
MiR-26b was also reported to be overexpressed during osteogenic differentiation of unrestricted somatic stem cells, which comprise a rare subpopulation in human cord blood [67]. [score:2]
MiR-26b also displayed low levels of expression in a human embryonic stem cell line (HUES-17) and in a colorectal cancer cell line with a high metastatic potential (LoVo) [64]. [score:2]
Yellow, high fold change in CD133 [+] patient sample as compared to its corresponding CD133 [−] paired sample; blue, high fold change in CD133 [−] sample compared to CD133 [+] paired sample The qRT-PCR results confirmed that five of the eight selected miRNAs had a differential expression between groups: miR-26b, miR-200c, miR-203, miR-363-3p, and miR-1825 (Fig.   2, p values and fold changes are provided in Table  2). [score:1]
Yellow, high fold change in CD133 [+] patient sample as compared to its corresponding CD133 [−] paired sample; blue, high fold change in CD133 [−] sample compared to CD133 [+] paired sample The qRT-PCR results confirmed that five of the eight selected miRNAs had a differential expression between groups: miR-26b, miR-200c, miR-203, miR-363-3p, and miR-1825 (Fig.   2, p values and fold changes are provided in Table  2). [score:1]
Loss of miR-26b also enhanced migration and invasion in oral squamous cell carcinoma [65]. [score:1]
Only hsa-miR-26b-5p, hsa-miR-363-3p, and hsa-miR-223-3p met these criteria. [score:1]
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[+] score: 57
Interestingly, the inhibition of miR-26b and overexpression of miR-128 had a synergistic effect on suppressing the tumorigenicity and invasiveness of pituitary tumors. [score:7]
Inhibition of miR-26b and overexpression of miR-128 suppressed colony formation and invasiveness of pituitary tumor cells. [score:7]
Specifically, five miRNAs (miR-26b, miR-26a, miR-212, miR-107, and miR-103) were upregulated and twelve miRNAs (miR-125b, miR-141, miR-144, miR-164, miR-145, miR-143, miR-15b, miR-16, miR-186, let-7b, let-7a3, and miR-128) were downregulated. [score:7]
Recently, Palumbo et al. identified miR-26b to be upregulated and miR-128 to be downregulated in GH-secreting pituitary tumors [18]. [score:7]
Since deregulation of PTEN and BMI1 correlates with the invasive and metastatic phenotype of several human cancer types [97, 98], it is possible that miR-26b and miR-128 regulate invasiveness of pituitary tumor cells by directly targeting PTEN and BMI1, respectively. [score:6]
miR-26b was found to be upregulated in GH-secreting pituitary tumors and directly regulate PTEN. [score:6]
miR-26b also targeted Lef-1 and increased Pit-1 expression in GH3 cells [57]. [score:5]
miR-26b and miR-128 controlled pituitary cell properties through regulation of their direct targets, PTEN, and BMI1, respectively [18]. [score:5]
miR-26b and miR-128 were found to directly regulate PTEN and BMI1, respectively. [score:3]
Therefore, miR-26b is able to regulate apoptosis through PTEN-Akt pathway. [score:2]
Since PTEN-Akt pathway plays important roles in cell cycle control, miR-26b and miR-128 might regulate cell cycle through PTEN-Akt pathway [71]. [score:2]
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12
[+] score: 42
Carrier DiseaseTarget miRNA (s) and role in cancer Viruses Adeno -associated viruses(AAV8)Hepatocellular cancer miR-26 tumor suppressor[140] Adenoviruses Lung cancer let-7 tumor suppressor[141] Adenoviruses Glioblastoma miR-145 tumor suppressor [144] Adenoviruses Glioblastoma miR-221-222 oncogene[145] Lentiviruses Prostate cancer miR-15-16 tumor suppressor[142] Lentiviruses Pancreatic cancer miR-21 oncogene [143] Lipid -based nanoparticles Cationic liposomes Breast cancer miR-34a tumor suppressor[124] Cationic liposomes Pancreatic cancer miR-34a, miR-143-145 tumor suppressors[146] Neutral lipid emulsion © Lung cancer miR-34a, let-7 tumor suppressors[147] Stable nucleic acid lipid particles Glioblastoma miR-21 oncogene[148] Polymer -based nanoparticles Polyurethane Glioblastoma miR-145 tumor suppressor[149] Poly(lactic-co-glycolic acid) Lymphoma miR-155 oncogene[96] Polyamidoamine Glioblastoma miR-21 oncogene[150] Viral vectors have also been applied in miRNA -based therapeutic strategies towards GBM. [score:21]
Carrier DiseaseTarget miRNA (s) and role in cancer Viruses Adeno -associated viruses(AAV8)Hepatocellular cancer miR-26 tumor suppressor[140] Adenoviruses Lung cancer let-7 tumor suppressor[141] Adenoviruses Glioblastoma miR-145 tumor suppressor [144] Adenoviruses Glioblastoma miR-221-222 oncogene[145] Lentiviruses Prostate cancer miR-15-16 tumor suppressor[142] Lentiviruses Pancreatic cancer miR-21 oncogene [143] Lipid -based nanoparticles Cationic liposomes Breast cancer miR-34a tumor suppressor[124] Cationic liposomes Pancreatic cancer miR-34a, miR-143-145 tumor suppressors[146] Neutral lipid emulsion © Lung cancer miR-34a, let-7 tumor suppressors[147] Stable nucleic acid lipid particles Glioblastoma miR-21 oncogene[148] Polymer -based nanoparticles Polyurethane Glioblastoma miR-145 tumor suppressor[149] Poly(lactic-co-glycolic acid) Lymphoma miR-155 oncogene[96] Polyamidoamine Glioblastoma miR-21 oncogene[150]Viral vectors have also been applied in miRNA -based therapeutic strategies towards GBM. [score:21]
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[+] score: 40
In total, 3 miRNAs were up-regulated in males miR-26b (A), miR-3162 (B) and miR-1268 (C), while 5 miRNAs were overexpressed in females; miR-720 (D), miR-186* (E), miR-3617 (F), miR-320c (G) and miR-3614-5p (H). [score:6]
Specifically, 3 miRNAs; miR-26b, miR-3162 and miR-1268 were consistently up-regulated in males, whilst 5 miRNAs including miR-720, miR-186*, miR-3617, miR-320c and miR-3614-5p were found overexpressed in females (Additional file 5: Figure S3). [score:6]
Specifically, 2 miRNAs; miR-720a and miR-891a were down-regulated and 6 miRNAs; miR320e, miR-3681, miR-601, miR-642a, miR-136 and miR-26b were overexpressed in the patient cohort when compared to the control group. [score:5]
Overall, 18 miRNAs were differentially expressed; 5 miRNAs were found up-regulated in the group of patients that are in complete remission when compared to the relapsed or the control groups; miR-3681 (A), miR-601 (B), miR-642a (C), miR-136 (D) and miR-26b (E). [score:5]
Based on our findings, following both initial and meta-analyses, we report the up-regulation of miR-3681, miR-34a, miR-136, miR-26b and miR-192 in the patient group, subsequently leading to the conclusion that they might possess oncogenic activities. [score:4]
In particular, miR-3681 (A), miR-642a (B), miR-26b (C), miR-136 (D) and miR-320e (E) were increased in alive samples as well as manifested linear regression with respect to expression moving from alive samples to controls. [score:3]
Based on the current findings, 8 miRNAs; miR-3681, miR-601, miR-320e, miR-34a, miR-642a, miR-136, miR-26b and miR-192 were found overexpressed in the patient group. [score:3]
Following our initial analysis, overall, 11 differentially expressed miRNAs were identified, including miR-1268, miR-2052, miR-26b, miR-3665, miR-3681, miR-3912, miR-519c-3p, miR-601, miR-608, miR-720 and miR-891a. [score:3]
Finally, two miRNAs were up-regulated as compared to the other groups: miR-2052 (J) and miR-26b (K). [score:3]
In total, 8 miRNAs were associated with patients’ clinical outcome; miR-3681, miR-601, miR-320e, miR-642a, miR-720, miR-891a, miR-136 and miR-26. [score:1]
However, the oncogenic role of miR-3681, miR-26b and miR-136 were validated with meta-analyses (Table  1). [score:1]
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14
[+] score: 40
d EZH2 siRNA transfection in HCC cells eliminated the difference in E-cadherin miR-26 overexpression and down-regulation Because EZH2 reportedly down-regulates E-cadherin expression [19, 25], we transfected our two HCC cell lines with EZH2 small interfering RNA (siRNA) to explore whether miR-26a could regulate E-cadherin expression by directly targeting EZH2 expression. [score:19]
d EZH2 siRNA transfection in HCC cells eliminated the difference in E-cadherin miR-26 overexpression and down-regulationBecause EZH2 reportedly down-regulates E-cadherin expression [19, 25], we transfected our two HCC cell lines with EZH2 small interfering RNA (siRNA) to explore whether miR-26a could regulate E-cadherin expression by directly targeting EZH2 expression. [score:19]
microRNA-26a (miR-26a), a member of the miR-26 family, has been considered to be a potential tumor suppressor in HCC [14, 15]. [score:2]
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15
[+] score: 39
miRNA Protein target(s) Regulatory Action Clinical Implications miR-1 LXRα*Directly suppresses LXR in vitro May promote an increase in cellular cholesterol[38] miR-9 ACAT1* Directly suppresses ACAT1 and esterification of cholesterol in macrophages Overexpression may promote macrophage cholesterol efflux and reduce foam cell formation[47] miR-10b ABCA1* ABCG1* Directly represses ABCA1 and ABCG1 expression and decreases macrophage cholesterol efflux Can be suppressed by dietary anthocyanins, leading to increased macrophage cholesterol efflux and lesion regression[63] miR-19b ABCA1* Directly suppresses ABCA1 and decreases cholesterol efflux to ApoA1; increases atherosclerotic lesion area and severity Inhibition may increase macrophage ABCA1, promoting cholesterol efflux and lesion regression[53] miR-26 ABCA1* ARL7 Activated by LXR to suppress both proteins, decreasing macrophage cholesterol efflux Inhibition may increase macrophage ABCA1, promoting cholesterol efflux and lesion regression[58] miR-27a/b ABCA1* ABCG1 ACAT1* CD36 LPL* Directly suppresses ABCA1, indirectly suppresses ABCG1, and reduces cholesterol efflux. [score:32]
LXR activation in vitro decreases the expression of miR-26 [58], reversing miR-26 -mediated suppression of ABCA1 and ADP-ribosylation factor-like 7 (ARL7), the transporter that carries cholesterol to the membrane to facilitate association with ABCA1 [59]. [score:5]
Sun D. Zhang J. Xie J. Wei W. Chen M. Zhao X. MiR-26 controls LXR -dependent cholesterol efflux by targeting ABCA1 and ARL7 FEBS Lett. [score:2]
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16
[+] score: 36
For the four miRNAs (miR-26a, miR-24, miR-26b, and miR-142-3p) chosen from the class of up-regulation in adults, their expression patterns were also confirmed by showing up-regulation (P < 0.0001) in the adults as compared to the preterm infants and the children, with three of them (miR-26a, miR-26b, and miR-24) being down-regulated from infancy to childhood (Fig. 3B). [score:11]
For the four miRNAs (miR-26a, miR-24, miR-26b, and miR-142-3p) chosen from the class of up-regulation in adults, their expression patterns were also confirmed by showing up-regulation (P < 0.0001) in the adults as compared to the preterm infants and the children, with three of them (miR-26a, miR-26b, and miR-24) being down-regulated from infancy to childhood. [score:11]
Fourth, miR-26a, miR-24, miR-26b, miR-410, and miR-107 were down-regulated from infancy to children, up-regulated in young adulthood, and then showed expression diminishing with aging (Fig. 4D). [score:9]
Six (miR-1, miR-486, miR-26a, miR-24, miR-26b, and miR-142-3p) of seven top 5% differentially expressed miRNAs in the classes with age-limited or age-related expression were confirmed in a validation set using qPCR. [score:5]
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17
[+] score: 32
To confirm the microarray hybridization results, qRT-PCR was performed on 8 up-regulated miRNAs (miR-335, miR-146b-5p, miR-26b, miR-30b, miR-21, miR-378, miR-143 and miR-148a) [10] and 3 down-regulated miRNA (miR-155,miR-221, and miR-1275), chosen on the basis of their levels of expression on the microarray and their biological significance. [score:9]
Additionally, our group [7] has also suggested that inhibited miR-26b inhibits adipogenic differentiation in human preadipocytes, and miR-335, as a potential adipogenic miRNA, is involved in adipose tissue inflammation and is highly expressed in mature 3T3-L1 [21]. [score:7]
Recent findings [7] have suggested that miR-26b inhibits adipogenic differentiation and overexpression of miR-1908 inhibited adipogenic differentiation [8]. [score:7]
Among these differentially expressed miRNAs, our group did further research for the adipogenic miRNAs in vivo and in vitro, including miR-148a [5], miR-26b [10], miR-146b [6] and miR-1275. [score:3]
We identified that miR-148a, miR-26b, miR-132, miR-365 and miR-1908 were highly expressed in mature adipocytes with over 5-fold compared to SVCs/hMSCs-Ad. [score:2]
Therefore, our present and previous studies bring in valuable information with respect to human obesity pathology because we have demonstrated that miR-148a, miR-146b, miR-26b and miR-335 are dysregulated in the process of adipocyte differentiation. [score:2]
In the present study, we found that hsa-miR-15a-5p, hsa-miR-106b-5p, hsa-miR-181a-5p, hsa-let-7 family, hsa-miR-27a-3p, hsa-miR-130b-3p, hsa-miR-152/148a-3p and hsa-miR-26b-5p got high degree means, which indicated that these miRNAs had a great weight in adipogenesis than others. [score:1]
As shown in Fig 6, hsa-miR-15a-5p, hsa-miR-106b-5p, hsa-miR-181a-5p, hsa-let-7 family, hsa-miR-27a-3p, hsa-miR-130b-3p, hsa-miR-152/148a-3p and hsa-miR-26b-5p got the highest degree means, which indicated that these miRNAs had more weight in adipogenesis than others. [score:1]
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18
[+] score: 29
These two miRs exhibit an opposite mechanism in regulating their respective targets: miR-26 mainly shows a direct correlation, which introduces to an indirect and difficult to unravel mechanism of regulation, whereas miR-34a displays a canonical down-regulation of its targets. [score:12]
In contrast, the most down-regulated miRNAs, miR-342-3p and miR-26b, showed a prevalence of positive correlations with their targets (respectively 8/9 and 20/22), which indicate a more complex and possible indirect relationship with the regulated genes. [score:8]
Network analysis identified in miR-34a and miR-26b the two main regulators in early (day 0 and day 7) or in late (day 14) phases of differentiation. [score:2]
Several microRNAs seem to regulate multiple genes of the TGFbeta pathway, like miR-760: SMAD4/SMURF1, miR-378: SMAD2/SMAD4/SOS1, miR-26b: SMAD2/4, miR-520e: AKT1/SMAD4. [score:2]
In parallel, we observed the modulation of several cancer-related microRNAs like miR-34a, miR-26b or miR-378. [score:1]
At initial (day 0) and middle (day 7) phases of differentiation miR-34a shows the highest number of correlated probes, instead miR-26b shows the highest number at an advanced stage of differentiation (day 14). [score:1]
Among the remaining 4 miRs (miR-26b, miR-34a, miR-342-3p, miR-520e), attention still points to miR-34a, which has the highest number (24) of predicted and correlated genes. [score:1]
Positive and significant correlations are 25.2 % and 22.1 % at days 0 and 7 respectively, while this percentage almost triplicates at day 14 (67.4 %) where a single miR, miR-26b, holds the majority of positive correlations (86/145) (Additional file 10: Figure S5). [score:1]
At advanced differentiation stages we observed a more interconnected mesh-like network, although miR-26b polarizes the majority of correlations. [score:1]
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19
[+] score: 25
Down-regulation of miR-144-3p, miR-181b-5p, miR-320a, miR-320c, miR-320d and miR-451a separated melanoma from normal skin; and down-regulation of miR-203, miR-205, miR-211 (and its homologue, miR-204), miR-23b, miR-26a and miR-26 distinguished melanoma from nevus. [score:7]
NS; and miR-203, miR-211-5p (and its homologue miR-204-5p), miR-205-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were down-regulated in PCM vs. [score:4]
NS libraries; and for miR-203, miR-204-5p (and its homologue, miR-211-5p), miR-205-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p down-regulated in PCM vs. [score:4]
Examining a specific KEGG pathway by down-regulation of miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p in melanoma highlighted the mitogen-activated protein kinase (MAPK) signaling pathway. [score:4]
For example, miR-205, miR-23b, miR-26a and miR-26b converge on PDGFRA or miR-211 and miR-204 converge on MAPK1, demonstrating a combinatorial effect of miRNAs on the same target. [score:3]
The expression profile of mature miRNAs for let-7a, let-7b, let-7c, let-7e, let-7f, let-7g and let-7i, miR-211, miR-27b, miR-26b, miR-126, miR-30d, miR-365, miR-150, miR451a and miR451a. [score:3]
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20
[+] score: 24
Known functions of the candidates are listed in Table 4. Table 4 Details of candidate endogenous control (EC) genes and their PCR amplification efficiencies Name Mature length (nt) RNA species Accession number Function Reference PCR Amplification efficiency (%) let-7a 22 miRNA MI0000060* Negatively regulates RAS oncogene[57] 96.3 miR-10b 22 miRNA MI0000267 * No functionally-verified targets 104.1 miR-16 22 miRNA MI0000070 * Negatively regulates B-cell lymphoma mRNA in chronic lymphocytic leukaemia patients[7] 104.3 miR-21 22 miRNA MI0000077 * Antiapoptotic, negatively regulates apoptosis-related genes[42] 96.8 miR-26b 22 miRNA MI0000084 * No functionally-verified targets 98.1 RNU19 198 snoRNA X94290 ** May be involved in pre-rRNA processing[59- 61] 99.2 RNU48 63 snoRNA NR_002745 ** Guides the 2'O-ribose methylation of 28S rRNA[62] 108.9 Z30 97 snoRNA AJ007733 ** Guides the methylation of the Am47 residue in U6 snRNA[63] 104.1 *mirBase database accession number ** Entrez gene ID Each reaction was primed using a gene-specific stem-loop primer. [score:7]
Known functions of the candidates are listed in Table 4. Table 4 Details of candidate endogenous control (EC) genes and their PCR amplification efficiencies Name Mature length (nt) RNA species Accession number Function Reference PCR Amplification efficiency (%) let-7a 22 miRNA MI0000060* Negatively regulates RAS oncogene[57] 96.3 miR-10b 22 miRNA MI0000267 * No functionally-verified targets 104.1 miR-16 22 miRNA MI0000070 * Negatively regulates B-cell lymphoma mRNA in chronic lymphocytic leukaemia patients[7] 104.3 miR-21 22 miRNA MI0000077 * Antiapoptotic, negatively regulates apoptosis-related genes[42] 96.8 miR-26b 22 miRNA MI0000084 * No functionally-verified targets 98.1 RNU19 198 snoRNA X94290 ** May be involved in pre-rRNA processing[59- 61] 99.2 RNU48 63 snoRNA NR_002745 ** Guides the 2'O-ribose methylation of 28S rRNA[62] 108.9 Z30 97 snoRNA AJ007733 ** Guides the methylation of the Am47 residue in U6 snRNA[63] 104.1 *mirBase database accession number ** Entrez gene ID Each reaction was primed using a gene-specific stem-loop primer. [score:7]
The expression of eight small RNAs was determined in 36 fresh-frozen breast tissues; three small nucleolar RNAs (snoRNAs, RNU19, RNU48 and Z30) and five miRNAs (let-7a, miR-10b, miR-16, miR-21 and miR-26b). [score:3]
MiR-30* expression was significantly different between the tissue subgroups (P < 0.05) except when using miR-26b as a single EC. [score:3]
MiR-16 and miR-21 showed relatively high expression with median Cts of 21, while let-7a, miR-10b, miR-26b and RNU48 were moderately abundant with median Cts of between 23 and 27. [score:3]
When normalised using miR-26b, ranked in the top four mosts Table 3 andidates by both geNorm and NormFinder (Table 2), no differences were detected between tissue groups. [score:1]
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21
[+] score: 23
To determine whether RSV G protein affected expression of the validated miRNAs (Fig. 1), A549 cells were infected (m. o. i. of 1) with recombinant RSV (6340WT) or with a recombinant RSV mutant virus lacking the G gene (RSVΔG), and expression of let-7f, miR-337, miR-520a, miR-26b and miR-24 was determined at 24 h p. i. Both 6340WT and RSVΔG replicated to similar levels over the short period of infection; however, in the absence of the G protein gene (RSVΔG), expression of let-7f was significantly (P<0.001) lower, whilst levels of miR-337 and miR-24 were significantly (P<0.05) upregulated (Table 1 and Fig. 2a). [score:10]
A549 cells were infected or mock infected with RSV 6340WT virus at an m. o. i. of 1 for 24 h. The data represent the mean qPCR fold change± sem of let-7f (let-7f), miR-337-3p (miR-337), miR-520a-5p (miR-520a), miR-24, miR-26b, miR-198 and miR-595 from three independent experiments relative to mock-infected cells, with values >1.0 considered to be upregulation and values below 1.0 considered to be downregulation. [score:5]
Expression of miR-520a was decreased slightly in RSVΔG-infected cells, but this change was not statistically significant, and miR-26b expression remained unchanged compared with 6340WT infection. [score:4]
In this mo del, microarray data validated by quantitative real-time PCR (qPCR) showed that a different set of miRNAs (let-7f, miR-337, miR-520a, miR-24, miR-26b, miR-198 and miR-595) was deregulated following RSV infection. [score:2]
qPCR performed using miRNA-specific oligonucleotides validated approximate inductions of twofold for miRNAs let-7f and miR-337, 1.7-fold for miR-520a and miR-24 (Fig. 1) and fourfold for miR-26b (Fig. 1). [score:1]
The miRNAs miR-24, miR-26b, miR-29a, miR-320a and miR-520a-5p (miR-520a) were also induced ≥1.5-fold, whilst miR-198, miR-224 and miR-595 were repressed by at least 1.5-fold (Table S1). [score:1]
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22
[+] score: 23
Expression of miR-26 in liver cancer cells in vitro induces cell cycle arrest via suppression of cyclin D2 and cyclin E2, and systemic administration of miR-26 in mouse HCC mo del induces inhibition of cancer cell proliferation and induction of tumor-specific apoptosis without toxicity [61]. [score:7]
Activation of this pathway also accounts for the gender differences and risk of HCC, as estrogen is known to suppress MyD88 -dependent IL-6 production, and miR-26 is expressed at a higher level in women than men in the liver [58, 59]. [score:5]
Patients whose tumors had low miR-26 expression had shorter survival but a better response to interferon therapy than did patients whose tumors had high expression of this miRNA [58]. [score:5]
However, as individual miRNAs regulate hundreds of transcripts, antiproliferative effects of miR-26 in HCC, might not attribute to a single oncogeneic pathway but a regulation of multiple pathways, such as c-Myc and p53 -dependent pathway. [score:3]
On the other hand, Ji, et al. showed that tumors with reduced miR-26 expression had a distinct transcriptomic pattern, with the activation of NF-κB and IL-6 signaling pathways [58]. [score:3]
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23
[+] score: 22
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-21, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-30a, hsa-mir-31, hsa-mir-96, hsa-mir-99a, hsa-mir-16-2, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-182, hsa-mir-183, hsa-mir-211, hsa-mir-217, hsa-mir-218-1, hsa-mir-218-2, hsa-mir-221, hsa-mir-222, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-132, hsa-mir-143, hsa-mir-145, hsa-mir-191, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-184, hsa-mir-190a, hsa-mir-195, rno-mir-322-1, rno-let-7d, rno-mir-335, rno-mir-342, rno-mir-135b, hsa-mir-30c-1, hsa-mir-299, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-379, hsa-mir-382, hsa-mir-342, hsa-mir-135b, hsa-mir-335, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-15b, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-26a, rno-mir-26b, rno-mir-30c-1, rno-mir-30e, rno-mir-30b, rno-mir-30d, rno-mir-30a, rno-mir-30c-2, rno-mir-31a, rno-mir-96, rno-mir-99a, rno-mir-125a, rno-mir-125b-1, rno-mir-125b-2, rno-mir-126a, rno-mir-132, rno-mir-143, rno-mir-145, rno-mir-183, rno-mir-184, rno-mir-190a-1, rno-mir-191a, rno-mir-195, rno-mir-211, rno-mir-217, rno-mir-218a-2, rno-mir-218a-1, rno-mir-221, rno-mir-222, rno-mir-299a, hsa-mir-384, hsa-mir-20b, hsa-mir-409, hsa-mir-412, hsa-mir-489, hsa-mir-494, rno-mir-489, rno-mir-412, rno-mir-543, rno-mir-542-1, rno-mir-379, rno-mir-494, rno-mir-382, rno-mir-409a, rno-mir-20b, hsa-mir-542, hsa-mir-770, hsa-mir-190b, hsa-mir-543, rno-mir-466c, rno-mir-17-2, rno-mir-182, rno-mir-190b, rno-mir-384, rno-mir-673, rno-mir-674, rno-mir-770, rno-mir-31b, rno-mir-191b, rno-mir-299b, rno-mir-218b, rno-mir-126b, rno-mir-409b, rno-let-7g, rno-mir-190a-2, rno-mir-322-2, rno-mir-542-2, rno-mir-542-3
Among the miRNAs examined, 79 miRNAs (24%) responded to the hyperandrogenic condition and interestingly, 80% of which were upregulated compared to the control group supporting the notion that hyperandrogenic condition down-regulates androgen receptors in the granulosa cells [35] which could be mediated by these upregulated miRNAs (rno-miR-379*, rno-let-7d, rno-miR-24, rno-miR-673, rno-miR-26b, rno-miR-335, rno-miR-382*, rno-miR-412, rno-miR-99a*, rno-miR-543, rno-miR-674-3p, rno-miR-409-3p). [score:9]
In addition to miR-221/222, several studies also highlighted the differential regulation of let-7d, let-7f, miR-25 and miR-26b in prostate and breast cancer, as well as in leukemia by the estrogen receptor pathways and that their expression was up-regulated in ERα -positive cells [50- 52]. [score:7]
A list of differentially expressed miRNAs (Fold change ≥ 2 and their corresponding P value) is presented in Figure  4. Beside this group, miRNAs which were also highly abundant in DHT -treated ovaries are rno-miR-221, rno-miR-222, rno-miR-25, rno-miR-26b, rno-miR-379*, rno-let-7d, rno-miR-24, rno-miR-673, rno-miR-26b, rno-miR-335, rno-miR-382*, rno-miR-412, rno-miR-99a*, rno-miR-543, rno-miR-674-3p, rno-miR-409-3p. [score:3]
Among the fourteen miRNAs mapped to the ingenuity databases, twelve (rno-let-7d, rno-miR-132, rno-miR-182, rno-miR-183, rno-miR-184, rno-miR-21, rno-miR-221, rno-miR-24, rno-miR-25, rno-miR-26b, rno-miR-31 and rno-miR-96) had 171 experimentally validated targets. [score:3]
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24
[+] score: 22
When the RNU6B expression using Sybr Green (performed on Rotor Gene Q) was compared to the results from same tissue from previous study (performed on ABI7900), the expression showed same stability, except that the Cq-values were higher in previous study for 2.38 ± 0.39. miR-26b showed similar expression to RNU6B in RNA later stored tissue (TaqMan or Sybr Green) as well as in FFPE samples (TaqMan), but it not seems to be suitable as RG, when validating FFPE using Sybr Green (SD is much higher when using miR-26b in comparison to RNU6B). [score:6]
RNU6B as RG with FFPE samples (Sybr Green) is in accordance to microarray results, and only expression of miR -122 relatively to miR-26b in FFPE samples corresponds to microarray results (Sybr Green). [score:3]
MicroRNAs, miR-122, miR-125a-5p, miR-125b, miR-126, miR-21 were tested relatively to RNU6B and miR-26b. [score:1]
It can be also noted from Table  5 that in the case of Sybr Green, using miR-26b as RG for FFPE samples gives different results from using RNU6B as RG. [score:1]
First, miR-26b was tested as RG in comparison to RNU6B. [score:1]
The results are summarized in Table  5. Using both technologies (TaqMan and Sybr Green), we confirmed most of the microarray results using RNU6B as RG, as well as using miR-26b (only in case of TaqMan approach). [score:1]
RNU6B and miR-26b were tested as the RGs. [score:1]
The results of miR-26b relatively to RNU6B were similar across the samples using either Sybr Green or TaqMan based approach, either FFPE or RNA later stored tissue samples (data not shown). [score:1]
In accordance to our previous studies [11, 33], miR-26b is as good RG, but only when using TaqMan technology. [score:1]
MicroRNAs, miR-1, miR-133a, miR-133b, and miR-98 were tested relatively to RNU6B, RNU48 and miR-26b. [score:1]
RNU6B, RNU48 and miR-26b were used as RGs, according to the manufacturer’s protocol. [score:1]
Legend: FFPE, formalin-fixed paraffin-embedded tissue; RNA later, samples stored in RNA later; RNU48, the small RNA RNU48 is used as RG; RNU6B, the small RNA RNU6B is used as RG; miR-26b, the miR-26b is used as RG. [score:1]
Both were used as RGs in our previous study [11], using miR-26b as RG in TaqMan based approach and RNU6B as RG in Sybr Green approach. [score:1]
In contrast, comparing miR-26b and RNU6B as RG, the different outcomes were detected in FFPE samples, but similar (and different from microarray study) in RNA later stored samples. [score:1]
In contrast, results from RNA later samples are similar between those that use RNU6B as RG and those that use miR-26b as RG. [score:1]
[1 to 20 of 15 sentences]
25
[+] score: 21
While downregulation of miR-26b has been observed in HNOC [25, 27], upregulation of miR-26b has been observed in bladder cancers [49], and polycythemia vera platelets [91]. [score:7]
It is worth knowing that Myc oncogene suppresses miR-26a, another member of the miR-26 family, which influences cell cycle progression by targeting the oncogene EZH2 in a murine lymphoma mo del [94]. [score:5]
Interestingly, miR-26 family members have been shown to be induced by hypoxia [92] and downregulated by exposure to cigarette smoke [93]. [score:4]
Also, downregulation of several microRNAs has been consistently observed in HNOC, including miR-26b, miR-138, miR-107, miR-139. [score:4]
The role of miR-26b in cancer is not clear. [score:1]
[1 to 20 of 5 sentences]
26
[+] score: 20
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-22, hsa-mir-26a-1, hsa-mir-98, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-15b, mmu-mir-101a, mmu-mir-126a, mmu-mir-130a, mmu-mir-133a-1, mmu-mir-142a, mmu-mir-181a-2, mmu-mir-194-1, hsa-mir-208a, hsa-mir-30c-2, mmu-mir-122, mmu-mir-143, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-181a-1, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-130a, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-142, hsa-mir-143, hsa-mir-126, hsa-mir-194-1, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-208a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-18a, mmu-mir-20a, mmu-mir-22, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29c, mmu-mir-98, mmu-mir-326, rno-mir-326, rno-let-7d, rno-mir-20a, rno-mir-101b, mmu-mir-101b, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-17, mmu-mir-19a, mmu-mir-181a-1, mmu-mir-26a-2, mmu-mir-19b-1, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-26a-2, hsa-mir-378a, mmu-mir-378a, hsa-mir-326, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, rno-let-7a-1, rno-let-7a-2, rno-let-7b, rno-let-7c-1, rno-let-7c-2, rno-let-7e, rno-let-7f-1, rno-let-7f-2, rno-let-7i, rno-mir-15b, rno-mir-16, rno-mir-17-1, rno-mir-18a, rno-mir-19b-1, rno-mir-19a, rno-mir-22, rno-mir-26a, rno-mir-26b, rno-mir-29c-1, rno-mir-30c-1, rno-mir-30c-2, rno-mir-98, rno-mir-101a, rno-mir-122, rno-mir-126a, rno-mir-130a, rno-mir-133a, rno-mir-142, rno-mir-143, rno-mir-181c, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-194-1, rno-mir-194-2, rno-mir-208a, rno-mir-181a-1, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-451a, mmu-mir-451a, rno-mir-451, ssc-mir-122, ssc-mir-15b, ssc-mir-181b-2, ssc-mir-19a, ssc-mir-20a, ssc-mir-26a, ssc-mir-326, ssc-mir-181c, ssc-let-7c, ssc-let-7f-1, ssc-let-7i, ssc-mir-18a, ssc-mir-29c, ssc-mir-30c-2, hsa-mir-484, hsa-mir-181d, hsa-mir-499a, rno-mir-1, rno-mir-133b, mmu-mir-484, mmu-mir-20b, rno-mir-20b, rno-mir-378a, rno-mir-499, hsa-mir-378d-2, mmu-mir-423, mmu-mir-499, mmu-mir-181d, mmu-mir-18b, mmu-mir-208b, hsa-mir-208b, rno-mir-17-2, rno-mir-181d, rno-mir-423, rno-mir-484, mmu-mir-1b, ssc-mir-15a, ssc-mir-16-2, ssc-mir-16-1, ssc-mir-17, ssc-mir-130a, ssc-mir-101-1, ssc-mir-101-2, ssc-mir-133a-1, ssc-mir-1, ssc-mir-181a-1, ssc-let-7a-1, ssc-let-7e, ssc-let-7g, ssc-mir-378-1, ssc-mir-133b, ssc-mir-499, ssc-mir-143, ssc-mir-423, ssc-mir-181a-2, ssc-mir-181b-1, ssc-mir-181d, ssc-mir-98, ssc-mir-208b, ssc-mir-142, ssc-mir-19b-1, hsa-mir-378b, ssc-mir-22, rno-mir-126b, rno-mir-208b, rno-mir-133c, hsa-mir-378c, ssc-mir-194b, ssc-mir-133a-2, ssc-mir-484, ssc-mir-30c-1, ssc-mir-126, ssc-mir-378-2, ssc-mir-451, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, mmu-mir-378b, mmu-mir-101c, hsa-mir-451b, hsa-mir-499b, ssc-let-7a-2, ssc-mir-18b, hsa-mir-378j, rno-mir-378b, mmu-mir-133c, mmu-let-7j, mmu-mir-378c, mmu-mir-378d, mmu-mir-451b, ssc-let-7d, ssc-let-7f-2, ssc-mir-20b-1, ssc-mir-20b-2, ssc-mir-194a, mmu-let-7k, mmu-mir-126b, mmu-mir-142b, rno-let-7g, rno-mir-15a, ssc-mir-378b, rno-mir-29c-2, rno-mir-1b, ssc-mir-26b
Thus, miRNA families (e. g., miR-1 and miR-122) that are specifically or highly expressed in any one of the 3 tissues, or miRNAs that are expressed ubiquitously (e. g., let-7 and miR-26) in all 3 tissues, show a far greater frequency than other miRNAs. [score:5]
The observation that miR-22, miR-26b, miR-126, miR-29c and miR-30c are ubiquitously expressed in 14 different tissues of pig is interesting. [score:3]
Additionally, many other miRNAs, such as let-7, miR-98, miR-16, miR22, miR-26b, miR-29c, miR-30c and miR126, were also expressed abundantly in thymus (Figure 3). [score:3]
miR-22, miR-26b, miR-29c, miR-30c and miR-126 exhibited almost similar expression patterns in all tissues examined (Figure 3B). [score:3]
For instance, let-7 is represented by 445 reads and miR-26 by 177 reads (Tables 1 and 2), and these two miRNAs are ubiquitously expressed in the heart, liver and thymus (Figure 3A and 3B). [score:3]
miR-22, miR-26b, miR-29c and miR-30c showed ubiquitous expression in diverse tissues. [score:3]
[1 to 20 of 6 sentences]
27
[+] score: 19
Other miRNAs from this paper: mmu-mir-26b
Knockdown of KPNA2 or ectopic expression of miR-26b could downregulate OCT4 [25]. [score:7]
Lin J, Zhang L, Huang H, Huang Y, Huang L, Wang J, et al. MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4. [score:5]
KPNA2 was validated as a direct target of miR-26b. [score:4]
Researchers have found that miR-26b/KPNA2/OCT4 axis inhibited epithelial ovarian cancer cells viability, migratory ability in vitro and in vivo. [score:3]
[1 to 20 of 4 sentences]
28
[+] score: 19
We identified five downregulated miRNAs (miR-26b, miR-125b, miR-203, miR-218, and miR-373) and one upregulated miRNA (miR-15a) when we compared miRNA expression in HNSCC cells versus primary human keratinocytes (Figure 1A). [score:8]
To assess the function of the deregulated miRNAs in HNSCC, we generated two YFP-luciferase -expressing cell lines—SCC13 (established facial SCC; Rheinwald and Beckett, 1981) and SJG15 (primary lingual SCC; Goldie et al., 2012)—in which we knocked down miR-15a or stably overexpressed miR-26b, miR-125b, miR-203, miR-218, or miR-373 using lentiviral approaches (Figure S1A). [score:7]
Overexpression of miR-26b and miR-218 enhanced metastatic dissemination, whereas the other four miRNAs had no significant effect (Figure 1D). [score:3]
Since the aim of the screen was to identify antimetastatic miRNAs, we did not analyze miR-26b and miR-218 further. [score:1]
[1 to 20 of 4 sentences]
29
[+] score: 19
The miR-26 family is also involved in hematopoiesis [9], and miR-423-5p and miR-103a have previously been shown to be downregulated in MDS and to have tumor suppressor properties [30, 31]. [score:6]
Host Gene Transcribed direction LFC Tumor Suppressor P-value let-7c-5p Canonical 21 MIR99AHG Same −2.13 Yes 0.001 let-7b-5p Canonical 22 MIRLET7BHG Same −2.49 Yes 0.002 let-7f-5p let-7f-1 let-7f-2 −1.4 Yes 0.004 Canonical 9 JB153432 Same Canonical x HUWE1 Same let-7a-5p let-7a-1 let-7a-2 let-7a-3 −1.67 Yes 0.005 Canonical 9 JB153432 Same Canonical 11 MIRLET100 Same Canonical 22 MIRLET7BHG Same hsa-miR-423-5p Canonical 17 NSRP1 Same −1.66 Yes 0.007 hsa-miR-103a-3p hsa-miR-103a-1 hsa-miR-103a-2 −0.87 Yes 0.009 Canonical 5 PANK3 Same Canonical 20 PANK2 Same hsa-miR-26b-5p Canonical 2 CTDSP1 Same −2.24 Yes 0.011 let-7i-5p Canonical 12 No host gene N/A −1.09 Yes 0.011 hsa-miR-15a-5p Canonical 13 DLEU2 Same −1.18 Unknown 0.011 hsa-miR-3605-5p Mirtron 1 PHC2 Same −1.23 Unknown 0.030 hsa-miR-192-5p Canonical 11 AB429224 Same −0.84 Yes 0.047 Abbreviations, Chr: Chromosome, LFC: log2 fold change. [score:4]
A weak but non-significant positive correlation between let7b and MIRLET7BHG (P = 0.08) was found, while no correlations were observed between the expression of CTDSP1 and miR-26b and between PANK2 and PANK3 and miR-103a. [score:3]
A weak but non-significant positive correlation between let-7b and MIRLET7BHG was observed (P = 0.08), while no correlations were observed between the expression of CTDSP1 and miR-26b and between PANK2 and PANK3 and miR-103a (Supplementary Figure S6). [score:3]
When considering all mutated samples together, eight miRNAs (let-7c-5p, let-7a-5p, let-7b-5p, miR-423-5p, let-7f-5p, miR-26b-5p, miR-15a-5p, and miR-3605-5p) were differentially expressed compared to wild-type samples. [score:2]
MIRLET7BHG is host gene for let-7b and CTDSP1 for miR-26b, while PANK2 and PANK3 host miR-103a-2 and miR-103a-1, respectively. [score:1]
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30
[+] score: 19
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-199a-2, hsa-mir-204, hsa-mir-210, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-193a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34b, hsa-mir-34c, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-363, hsa-mir-365a, hsa-mir-365b, hsa-mir-369, hsa-mir-370, hsa-mir-371a, hsa-mir-375, hsa-mir-378a, hsa-mir-133b, hsa-mir-423, hsa-mir-448, hsa-mir-429, hsa-mir-486-1, hsa-mir-146b, hsa-mir-181d, hsa-mir-520c, hsa-mir-499a, hsa-mir-509-1, hsa-mir-532, hsa-mir-33b, hsa-mir-637, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-509-2, hsa-mir-208b, hsa-mir-509-3, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-371b, hsa-mir-499b, hsa-mir-378j, hsa-mir-486-2
Overexpression of miR-26b in 3T3-L1 cells significantly accelerated the mRNA expression of adipogenic markers, PPARγ, fatty acid synthase (FAS), C/EBPα, and lipoprotein lipase, and increased lipid accumulation, by inhibiting the PTEN expression. [score:9]
In contrast, inhibition of miR-26b expression decreased cell differentiation [81]. [score:5]
Li G, Ning C, Ma Y, Jin L, Tang Q, Li X, Li M, Liu H: miR-26b promotes 3T3-L1 adipocyte differentiation through targeting PTEN. [score:3]
Another miRNA involved in the regulation of adipogenic differentiation is miR-26b [81]. [score:2]
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31
[+] score: 18
Moreover, miR-720 was up-regulated and miR-26b-5p down-regulated in isolated glomeruli of murine diabetic nephropathy 42. [score:7]
For the detection of differentially expressed microRNAs we analyzed 240 target miRNAs with four different normalization methods: Recommendation of (i) geNormPlus (geometric mean of miR-26b-5p and miR-195-5p (Pool A) as well as of miR-720, miR-1274a, miR-1260a and miR-30a-5p (Pool B)), (ii) NormFinder (geometric mean of miR-28-5p, miR-127-3p and miR-181a-5p (Pool A) as well as miR-10b-3p, miR-181a-2-3p and miR-720 (Pool B)), (iii) global mean normalization method, (iv) two most stable snoRNAs (geometric mean of RNU44 and RNU48 (Pool A) as well as RNU48 and snRNU6 (Pool B)) or (v) geometric mean of all three snoRNAs provided by the manufacturer. [score:5]
In order to provide a set of reference miRNAs one could suggest the intersection of the best 15 reference genes from both algorithms geNormPlus and NormFinder (miR-10b-3p, miR-1260a, miR-127-3p, miR-1274a, miR-181a-5p, miR-181a-2-3p, miR-195-5p, miR-26b-5p, miR-28-5p, miR-30a-3p, miR-30a-5p, miR-30d-5p, miR-361-5p, miR-720, miR-92a-3p). [score:1]
Therefore miRNA-195-5p, miR-26b-5p and miR-720 should be used with caution or completely avoided as reference transcripts in diabetic subjects. [score:1]
GeNormPlus recommended miR-26b-5p and miR-195-5p (Pool A) as well as miR-720, miR-1274a, miR-1260a and miR-30a-5p (Pool B) as the best combinations (Fig. 2). [score:1]
Several miRNAs like miR-181a-5p, miRNA-195-5p, miR-720, and miR-26b-5p have been described in other studies. [score:1]
Relative expression levels were calculated using the following normalization methods: geNormPlus (miR-26b, miR-195-5p) NormFinder (miR-28-5p, miR-127-3p, miR-181a-5p), global Mean, best two snRNAs (RNU44, RNU48) and all 3 snRNAs (RNU44, RNU48, snRNU6). [score:1]
Based on our analysis we suggest miR-26b-5p (best according to geNormPlus) and miR-28-5p (best according to NormFinder) and one snoRNA (RNU44) as suitable reference genes choice for human glomerular miRNA quantification in IgA nephropathy. [score:1]
[1 to 20 of 8 sentences]
32
[+] score: 18
The panel of differentially expressed miRNAs were validated by real-time PCR using TaqMan assays, and the results were consistent with the data that showed up-regulation of miR-21, miR-221, miR-100 and miR-26a and down-regulation of miR-26b, miR-141, miR-96, miR483-3p, miR-216, and miR-217 in the KC compared to control mice (Figure 1A). [score:7]
We have shown that in tumor samples compared to normal samples, the majority of miRNAs (miR-216, miR-217, miR-100, miR-345, miR-141, miR-483-3p, miR-26b, miR-150, Let-7b, Let-195 and miR-96) were downregulated, and few were upregulated (miR-146b, miR-205, miR-31, miR-192, miR-194 21, miR-379, miR-431, miR-541, and miR-199b). [score:6]
Further, at 50 weeks of age, the expression of miR-216, miR-217, miR-345, miR-141, miR-483-3p, miR-26b, miR-96, Let-7b (p-value = 0.01), miR-100, miR-26a and miR-150 (p-value = 0.094) were further downregulated in KC animals compared to control mice (Figure 2D). [score:5]
[1 to 20 of 3 sentences]
33
[+] score: 17
The most significant downregulation was observed for tumor suppressive miRNAs of the, miR-26, -30 and -200 families. [score:6]
Vice versa, the adenoviral delivery of the tumor-suppressive miR-26 was shown to suppress mouse liver tumorigenesis [33]. [score:5]
The three tumor-suppressive miRNA-families miR-26 [31], -30 [38] and [27] were suggested to be expressed at lower levels in PTCs. [score:5]
Our recent analyses confirmed these observations for the miR-26 and families [30]. [score:1]
[1 to 20 of 4 sentences]
34
[+] score: 17
Recently, Luo et al. [28] found that miR-26 family members were significantly downregulated (>50%) in LAAs from a canine AF mo del (miR-26a) and in right atrial appendages from AF patients (miR-26a and miR-26b). [score:4]
A recent study identified miR-26 as a potentially important regulator of KCNJ2 gene expression and, via I [K1], a determinant of AF susceptibility [28]. [score:4]
030hsa-miR-21-5p442.29819.400.890.047hsa-miR-44974574.246545.730.520.047Downregulated*hsa-miR-26a-5p9701.874313.64-1.170.007hsa-miR-112740.133079.47-2.050.019hsa-miR-195-5p611.70384.70-0.670.022hsa-miR-26b-5p794.41198.33-2.000.023hsa-miR-5100775.16362.75-1.100.029hsa-miR-29a-3p589.33512.76-0.200. [score:4]
Studies have shown that miRNAs may be involved directly or indirectly in AF by modulating atrial electrical remo deling (miR-1, miR-26, miR-328) [10, 27, 28] or structural remo deling (miR-30, miR-133, mir-590) [7, 30]. [score:3]
In addition, it also identified miR-26 as a potential mediator of the electrophysiological effects of Ca [2+] -dependent NFAT (nuclear factor of activated T cells) signaling, believed to be important in the perpetuation of AF. [score:1]
The results of our study and that of Xiao et al. [16] were completely different, except for miR-26b. [score:1]
[1 to 20 of 6 sentences]
35
[+] score: 17
Recent works have reported that miR-101 downregulation is involved in COX-2 overexpression in human colon cancer cells (CRC) [24], miRNA-26b regulates the expression of COX-2 in desferrioxamine -treated carcinoma of nasopharyngeal epithelial cells [25] and binding of miR-16 to AREs of TNF-α, IL-6, IL-9 and COX-2 mRNA transcripts could promote their degradation [20], [26]. [score:9]
The miRNAs (miR-16, miR-26b, miR-101, miR-199a, miR-122 and miR-21) were selected by using miRWalk computational analyses, that covers miRNA-targets interactions information produced by 8 established miRNA prediction programs on 3' UTRs of all known genes of Human, Mouse and Rat, i. e., RNA22, miRanda, miRDB, TargetScan, RNAhybrid, PITA, PICTAR, and Diana-microT, and comparing the obtained results with data collected from the literature. [score:5]
The expression profile of six miRNAs (miR-16, miR-26b, miR-101, miR-199a, miR-122 and miR-21) was analyzed in HCC cell lines (Table 1). [score:3]
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36
[+] score: 16
The 4HPR treatment increased the expression of miR-16, miR-26b, miR-23a, and miR-15b in ARPE-19 cells, although these increases were modest when compared to the increase in the expression of miR-9. Our studies demonstrate that miR-9 is expressed in the RPE cell line ARPE-19, and its expression is increased by a retinoic acid derivative and by an inhibitor of promoter hypermethylation. [score:10]
The 4HPR treatment also significantly increased the expression of miR-15b, miR-16, miR-23a, and miR-26b. [score:3]
Increases in the expression of miR-16, miR-26b, miR-23a, and miR-15b were observed following 4HPR treatment; however, these increases were modest when compared to the approximately twofold increase observed for miR-9. The 5′-flanking regions (~1 kb) of genes generating miR-16, miR-26b, miR-23a, miR-15b, miR-223, and let-7a were analyzed for the presence of consensus binding sites for CEBP-α and CEBP-β. [score:2]
However, putative binding sites for CEBP-α and CEBP-β were absent in the promoter regions of the genes encoding miR-23a and miR-26b. [score:1]
[1 to 20 of 4 sentences]
37
[+] score: 16
Median miR-26b expression was highest during T5 (ΔCT = 0.11), increasing from T1 (ΔCT = 0.85) and decreased at T8 (ΔCT = 1.46; Table  3, Fig.   2). [score:3]
In case of missing values (VAS, miR-26b and miR-134), the Skillings-Mack test was used as a replacement for the Friedman test to take advantage of all available data [56]. [score:1]
The concentration of alpha-amylase was negatively correlated weakly to moderately with the ΔCT-values of miR-21 (r = −0.34, p < 0.001; Fig.   4A) and miR-26b (r = −0.28, p < 0.01; Fig.   4B), i. e., the higher alpha-amylase, the higher the miRNA-concentration or the epigenetic reaction, respectively. [score:1]
The ΔCT-values of miR-29a strongly correlate with miR-20b (r = 0.62, p < 0.001; Fig.   5E), miR-21 (r = 0.63, p < 0.001; Fig.   5F) and miR-26b (r = 0.71, p < 0.001; Fig.   5G), and weakly to moderately with miR-16 (r = 0.28, p < 0.01; Fig.   5D) and miR-134 (r = 0.33, p < 0.05; Fig.   5H). [score:1]
Of these, three miRNAs showed significant changes across the test procedure: miR-20b (p [Skillings-Mack] < 0,05), miR-21 (p [Friedman] < 0,05) and miR-26b (p [Skillings-Mack] > 0,001). [score:1]
Furthermore, miR-26b and miR-16 were positively interrelated, too (r = 0.36, p < 0.001; Fig.   5B). [score:1]
Figure 4 Correlations between alpha-amylase and miR-21/miR-26b. [score:1]
Although an association of miR-26b-concentrations with sympathetic activation might be suggested by its significant correlation with the concentration of salivary alpha-amylase in our study, such an association could not be found in current literature. [score:1]
In the study of Honda et al., the concentrations of miR-16, miR-20b, miR-26b and miR-29a assessed in whole blood were increased in healthy male students who perceived chronic mental stress due to an upcoming examination as a psychological stressor [22]. [score:1]
miR-21 and miR-26b showed a strong correlation (r = 0.84, p < 0.001; Fig.   5C), i. e., if the ΔCT-values of miR-21 were high, it was very likely that the same was true for miR-26b. [score:1]
However, this assumption is corroborated by the significant correlation between miR-26b and miR-21, a miRNA also highly assumed to be associated with the sympathetic activation [32]. [score:1]
Previously, miR-16 and miR-26b had been reported to be associated with psychological stress responses or psychiatric disorders [38]. [score:1]
Namely, miR-21 and miR-26b appear to be associated with the sympathetic activation. [score:1]
miR-26b has been described to be associated with neurogenesis [42] and to be decreased in patients with hepatocellular carcinoma [43]. [score:1]
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[+] score: 16
miR-26b, which is regulated by glucose levels [47], is required for adipogenesis and target Pten and Adam17 [45, 46]. [score:4]
miR-26b is required for adipogenesis and target Pten and Adam17 [45, 46]; moreover, it is also regulated by glucose levels [47]. [score:4]
By contrast, miR-26b-5p, miR-199a-3p, miR-377–3p, miR-let-7f-5p, miR-200a-3p, miR-21–5p, miR-152–3p, and miR-192–5p expressions were repressed by SO diet consumption. [score:3]
miR-26b-5p expression was lower after FO compared with PO diet. [score:2]
Similarly, miR-215 expression decreased after FO compared to OO and PO diets and miR-26b-5p expression decreased after FO compared with PO diet and miR-9a-5p after FO compared with SO diet. [score:2]
Likewise, we observed a decrease in the expression of several hepatic miRNAs, namely miR-192–5p, miR-10b-5p, miR-377–3p, and miR-215 after FO compared with OO and PO diets and miR-21–5p and mir-26b-5p after FO compared with PO diets. [score:1]
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[+] score: 16
miR-26b down-regulation could suppress cell proliferation, cell-cycle transition and migration by targeting TRAF5 [35]. [score:8]
miR-26b expression was abnormally up-regulated in esophageal cancer cells and human tissue, whereas no significant change was found on miR-26a expression. [score:8]
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40
[+] score: 15
With an aim towards uncovering new candidates for therapeutic targeting, we over-expressed miR-26b in vitro, which, while not our top significant miRNA, was correlated with better prognosis (P<0.05), as well as previously shown as inducing apoptosis in breast cancer [23]. [score:5]
Over -expression and MTS experiments for miR-26b were carried out in the same manner as for the miR-29a experiments of Figure 6D. [score:3]
Interestingly, miR-26b inhibited proliferation of HEYA8 but not OVCAR-8 cells (Figure S5, both cell lines being derived from ovarian cancers), though cell line-specific effects of miRNAs in ovarian cancer have been reported previously (possibly reflecting genotypic differences) [10]. [score:3]
Univariate Cox test evaluates miR-26b expression as a continuous variable; Log rank test compares the top 25% of expressors with the rest of the patients. [score:3]
Figure S5 miR-26b, associated with longer survival in ovarian cancer patients, impacts cell viability in vitro in HEYA8 cell line but not in OVCAR8. [score:1]
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[+] score: 14
Twelve of them (miR-10b, miR-15a, miR-19a, miR-26b, miR-30a, miR-30c, miR-125a, miR-125b, miR-148a, miR-148b, miR-195 and miR-320) are down-regulated both in dogs and in humans whereas one (miR-494) is up-regulated in both species and four (miR-29a, miR-181a, miR-196a and miR-374a) are down-regulated in dogs but up-regulated in humans. [score:13]
PCA plot reveals the distinct sample clusters for metastatic tumours and non-metastatic tumours The following ten microRNAs were selected for validation of microarray results: cfa-let-7c, cfa-miR-10b, cfa-miR-26a, cfa-miR-26b, cfa-miR-29c, cfa-miR-30a, cfa-miR-30b, cfa-miR-30c, cfa-miR-148a and cfa-miR-299. [score:1]
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42
[+] score: 13
Other miRNAs from this paper: hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26a-2
The relative locations of RNA editing sites, miRNA target sites, as well as the predicted RNA secondary structures are illustrated in Fig.   7b, c. Both genes were confirmed as miRNA target genes (miR-24 targeting GOLGA3 and miR-26 targeting GINS1) (Supplementary Fig.   11,). [score:9]
To make miRNA sponge vectors, three copies of miR-24 and miR-26 target sequences were inserted into the 3′ UTR of a GFP reporter via EcoRI and BamH I cloning sites (Supplementary Table  2). [score:3]
A total of 2.5 μg miR-24 or miR-26 sponge vector were transfected into HEK293 cells. [score:1]
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[+] score: 13
In contrast, three of the measured targets were significantly down-regulated during acute FMDV infection: bta-let-7 g (−1.96 fold decrease), bta-miR-1281 (−2.50 fold decrease), and bta-miR-26b (-3.09 fold decrease) (Table  2 and Fig.   2a). [score:4]
In contrast, the ViTa algorithm found that more of these miRNAs could potentially target the genome, adding bta-miR-205, bta-miR-26b, bta-let-7 g, bta-miR-34a, bta-miR-144, bta-miR-181b, and bta-miR-147 to the list. [score:3]
Of the differentially regulated miRNAs, 16 (bta-miR-23b-5p, let-7 g, bta-miR-22-5p, bta-miR-1224, bta-miR-144, bta-miR-497, bta-miR-455-3p, bta-miR-154a, bta-miR-369-3p, bta-miR-26b, bta-miR-34a, bta-miR-205, bta-miR-181b, bta-miR-146a, bta-miR-17-5p, and bta-miR-31) have previously been described to play a role in cellular proliferation or apoptosis (Fig.   6b, orange circle). [score:2]
The non-clustered miRNAs included: let-7 g, bta-miR-26b, bta-miR-150, bta-miR-34a, bta-miR-146a, bta-miR-147, bta-miR-205, bta-miR-455-3p, bta-miR-1224, bta-miR-1281, and bta-miR-31. [score:1]
The remaining 8 miRNAs are encoded within intronic regions: bta-miR-26b, bta-miR-455-3p, bta-miR-23b-5p, bta-let-7 g, bta-miR-22-5p, bta-miR-147, bta-miR-369-3p, and bta-miR-1224. [score:1]
Nine of the miRNAs (bta-miR-26b, bta-miR-34a, bta-miR-205, bta-miR-181b, bta-miR-146a, bta-miR-17-5p, bta-miR-31, bta-miR-150, and bta-miR-147), have been ascribed immune modulatory functions (Fig.   6b, blue circle). [score:1]
Also notable is that five of the detected miRNAs (bta-miR-1281, bta-miR-369-3p, bta-miR-26b, bta-miR-34a, and bta-miR-205) are involved in adipogenesis or other lipid metabolic pathways (Fig.   6b, green circle). [score:1]
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[+] score: 12
Other miRNAs from this paper: mmu-mir-26b
For instance, inhibition of Rb in primary cortical neurons by miR-26b, a microRNA highly expressed in pathological areas in the human brain in AD, leads to aberrant CCE with increased vulnerability to tau hyperphosphorylation (another hallmark of AD pathology) and subsequent cell death mediated by pro-apoptotic downstream targets including E2F genes and cyclin E1 (Absalon et al., 2013). [score:7]
MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau-phosphorylation, and apoptosis in postmitotic neurons. [score:5]
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45
[+] score: 12
To validate the microarray data, we selected 3 miRNAs (miR-10b-5p, miR-1471 and miR-199a-5p) that were downregulated in pNK cells and 3 miRNAs (miR-181a-2-3p, miR-26b-3p and miR-362-5p) that were upregulated in human pNK cells for RT-PCR confirmation. [score:7]
Red and green pseudocolors indicate transcripts levels below or above the mean, respectively, on a log 2 scale representing gene expression ratios from 0 to 6. (c) Real-time PCR analysis of the expression of miR-10b-5p, miR-1471, miR-199a-5p, miR-181a-2-3p, miR-26b-3p, and miR-362-5p. [score:5]
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46
[+] score: 12
Within the genetic background scanned for miRNA expression on Exiqon arrays, miR-24 and miR-26b were significantly correlated with GH and PRL, with miR-26b being reported to have a potential impact upon expression of the TF Pit-1 in GH3 cells by inhibiting the Pit-1 inhibitor called Lef-1 [59]. [score:9]
Correlation analysis shows the miR-26b expression is also related to GH and PRL transcript levels (Fig 6D), with relationships between this microRNA and TF’s discussed below. [score:3]
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47
[+] score: 12
AKT1, a protein kinase B, known to be downregulated in schizophrenia, is also regulated by miR-26b, the second most abundant microRNA, and both proteins interact with ATF2, activating transcription factor 2, which is also hypermethylated in schizophrenics in [6]. [score:5]
Protein-coding genes that interact with each other according to STRING, are associated with schizophrenia and regulated by mir-335 or mir-26b, are shown in Fig.   3. The network contains two main hubs, AKT1 and GABBR1, which, although do not have a direct interaction, both interact with ATF2. [score:3]
Fig. 3Protein targets of mir-335 and mir-26b and their known interactions according to STRING v9.1 [8], constructed by Cytoscape. [score:3]
First 10 miRNAs: miR-335-5p, miR-26b-5p, miR-16-5p, miR-124-3p, miR-92a-3p, miR-484, miR-155-5p, let-7b-5p, miR-193b-3p, miR-21-5p. [score:1]
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[+] score: 12
Luo et al. [13] identified miR-26 as a potentially important regulator of KCNJ2 gene expression and, via I [K1], a determinant of AF susceptibility. [score:4]
28E-02hsa-miR-331-3p1402470.826.46E-02hsa-miR-149-3p961630.776.79E-02hsa-miR-181a-5p105716130.618.50E-02hsa-miR-30a-5p2493760.596.94E-02hsa-miR-197374511230.596.02E-02hsa-miR-4497457465460.524.68E-02Down-regulated (n = 20*)hsa-miR-1127403079−2.051.94E-02hsa-miR-26b-5p794198−2.002.30E-02hsa-miR-44541262488−1.373.93E-02hsa-miR-361-5p652259−1.333.53E-02hsa-miR-151a-5p694302−1.203.90E-02hsa-miR-26a-5p97024314−1.177.22E-03hsa-miR-378a-3p683307−1.157.26E-02hsa-miR-5190311141−1.149.06E-02hsa-miR-5100775363−1.102.89E-02hsa-miR-151b609288−1.086. [score:4]
Studies have shown that miRNAs may be involved directly or indirectly in AF by modulating atrial electrical remo deling (i. e. miR-1, miR-26, and miR-328) or structural remo deling (i. e. miR-30, miR-133, and mir-590). [score:3]
42E-02hsa-miR-145-5p72843352−1.128.73E-02hsa-miR-378a-3p477221−1.118.70E-02hsa-miR-30b-5p1857869−1.105.33E-02hsa-miR-26b-5p1342638−1.075.00E-02hsa-miR-133b39121868−1.079.81E-02hsa-miR-107592284−1.063.95E-02hsa-miR-152293141−1.057.94E-02hsa-miR-30a-5p409201−1.032.72E-02hsa-miR-125b-5p76023820−0.997.43E-02hsa-miR-4286243128−0.928.45E-02hsa-miR-191-5p1441767−0.917.19E-02hsa-miR-26a-5p96215219−0.886.04E-02hsa-miR-21-5p633351−0.858.92E-03hsa-miR-30d-5p1225692−0.825.79E-02hsa-miR-5100458274−0.748.76E-02hsa-miR-181a-5p998613−0.703. [score:1]
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[+] score: 12
Among miR-26 targets, genes with the highest level of down-regulation were MSMO1 and VMA21. [score:6]
regulated kinase 1A) 2.0 PPP1R16A (protein phosphatase 1, regulatory subunit 16A) 2.0Among the miRNAs that have been individually shown to be important for both CL function and adiposity, changes in miR-26 and miR-28 were notable. [score:3]
regulated kinase 1A) 2.0 PPP1R16A (protein phosphatase 1, regulatory subunit 16A) 2.0 Among the miRNAs that have been individually shown to be important for both CL function and adiposity, changes in miR-26 and miR-28 were notable. [score:3]
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50
[+] score: 12
miR-125b, miR-126, miR-10b, miR-10a and miR-191 were underexpressed in cancer samples, whereas miR-26b, miR-607 and miR-135b were overexpressed. [score:5]
In fact, miR-125b, miR-126, miR-10b, miR-10a and miR-191 were underexpressed whereas miR-26b, miR-607 and miR-135b were overexpressed in cancer samples examined, in comparison with the gynecomastia samples. [score:5]
analysisTo confirm the results of microarray analysis, we performed quantitative real-time PCR analysis on a limited number of samples (19 cancer samples, five gynecomastia samples) using probes corresponding to miR-125b, miR-126, miR-10b, miR-10a, miR-191, miR-26b, miR-607 and miR-135b (Figure 2). [score:1]
To confirm the results of microarray analysis, we performed quantitative real-time PCR analysis on a limited number of samples (19 cancer samples, five gynecomastia samples) using probes corresponding to miR-125b, miR-126, miR-10b, miR-10a, miR-191, miR-26b, miR-607 and miR-135b (Figure 2). [score:1]
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51
[+] score: 11
It has been found that, in chronic gastritis, the expression of miR-1 and miR-155 is upregulated, whereas the expression of miR-20, miR-26b, miR-202, miR-203, and miR-205 is downregulated. [score:11]
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[+] score: 11
Similarly, miRNAs that were up-regulated in other cancers such as miR-126 in colon cancer [30], miR-23a and miR-125b in HCC [33, 34], miR-191 and miR-199a in myeloid leukemia [35], miR-200b [36], miR-10b and miR-26b in breast cancer [37, 38], and miR-98 [28] in head and neck squamous cell carcinoma were also up-regulated in rabbit VX2 tumors. [score:7]
miR-26b, miR-23b, miR-203, and miR-23a were significantly up-regulated in bladder cancers [32]. [score:4]
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[+] score: 11
In addition, miR-26b inhibited the VM processes accompanied with the downregulation of EphA2 proteins, which revealed that EphA2 was correlated with the capability of VM formation in gliomas. [score:6]
Wu et al (31) found that ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. [score:5]
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[+] score: 11
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-139, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-190a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-429, hsa-mir-491, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, hsa-mir-517a, hsa-mir-500a, hsa-mir-376a-2, hsa-mir-92b, hsa-mir-33b, hsa-mir-637, hsa-mir-151b, hsa-mir-298, hsa-mir-190b, hsa-mir-374b, hsa-mir-500b, hsa-mir-374c, hsa-mir-219b, hsa-mir-203b
Izzotti et al. (2009a, b) have monitored the expression of 484 miRNAs in the lungs of mice exposed to cigarette smoking, the most remarkably downregulated miRNAs belonged to several miRNA families, such as let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223. [score:6]
Zhang and Pan (2009) have evaluated the effects of Hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine (also known as hexogen or cyclonite) (RDX) on miRNA expression in mouse brain and liver, most of the miRNAs that showed altered expression, including let-7, miR-17-92, miR-10b, miR-15, miR-16, miR-26, and miR-181, were related to toxicant-metabolizing enzymes, and genes related to carcinogenesis, and neurotoxicity, in addition, consistent with the known neurotoxic effects of RDX, the authors documented significant changes in miRNA expression in the brains of RDX -treated animals, such as miR-206, miR-30a, miR-30c, miR-30d, and miR-195. [score:5]
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[+] score: 11
92) 43 hsa-mir-302a dbDEMC 19 hsa-let-7g dbDEMC, miR2Disease 44 hsa-mir-212 literature 20 hsa-let-7b dbDEMC, HMDD, miR2Disease 45 hsa-mir-372 dbDEMC 21 hsa-mir-150 dbDEMC, literature 46 hsa-mir-197 dbDEMC 22 hsa-mir-338 dbDEMC 47 hsa-mir-124 literature 23 hsa-mir-103 dbDEMC, miR2Disease 48 hsa-mir-378 HMDD 24 hsa-mir-15b dbDEMC, HMDD 49 hsa-mir-26b dbDEMC, miR2Disease 25 hsa-mir-31 dbDEMC, HMDD, miR2Disease 50 hsa-mir-542 higher RWRMDA (No. [score:11]
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Strong inverse correlation was observed between the tumor suppressor PTEN and several members of the miR-17, miR-19, miR-130/301 and miR-26 families, which were upregulated in the osteosarcoma cell lines. [score:6]
In addition, the expression of the tumor suppressor gene phosphatase and tensin homolog (PTEN) inversely correlated with miR-17, miR-20b, miR-9* and miR-92a (Table 2), but also showed a modest inverse correlation (r = −0.4 to −0.5) with other miRNAs of the miR-17, miR-19, miR-130/301 and miR-26 families (Table S6). [score:5]
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66, 67, 68, 69, 70, 71 MALAT1 is upregulated and acts as a sponge for miR-26b to upregulate its target ULK2 in cerebral I/R injury. [score:9]
[71] In light of the protective effect of autophagy against I/R in brain microvascular endothelial cells, the enhanced activity of the MALAT1/miR-26b/ULK2 regulatory axis appears to be a self-defense mechanism in response to ischemic stroke, the pathological basis of which is I/R injury. [score:2]
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[+] score: 11
Highest-ranking miRNAs included miR-16/15a (46 targets), miR-27b (44 targets), let-7f (35 targets), miR-26b (33 targets), and miR-25 (30 targets). [score:11]
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59
[+] score: 11
We found that ten of the down-regulated miRNAs (miR101, miR26a, miR26b, miR30a, miR30b, miR30d, miR30e, miR34b, miR-let7 g and miRN140) were grouped together in a functional network (Figure 3A) and nine of the down-regulated miRNAs (miR-130a, miR-133a, miR-142, miR-150, miR15a, miR-16, miR-29b, miR-30c and miR-99a) were grouped together in a second network (Figure 3B). [score:7]
With the aid of IPA pathway designer, we found that 27 of the 31 down-regulated miRNAs were linked to one or more mRNA networks and 20 of them (let-7 g, miR-101, miR-126, miR-133a, miR-142-5p, miR-150, miR-15a, miR-26b, miR-28, miR-29b, miR-30a, miR-30b, miR-30c, miR-30d, miR-30e, miR-34b, miR-99a, mmu-miR-151, mmu-miR-342 and rno-miR-151) were involved in all of the top 4 networks. [score:4]
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60
[+] score: 10
Notably the microRNAs upregulated in the control fascia accounting for the greatest differential in read count are heavily enriched in previously validated anti-fibrotic extracellular matrix targeting microRNAs (Table  1), including let-7 [23– 25], miR-29a-3p [26], miR-26b-5p, miR-30d-5p [27, 28], miR-27a-3p, miR-27b-3p [29, 30], miR-10a-5p [31], miR-26a-5p [32– 35], miR-101-3p [36– 39], and miR-10b-5p [40], as well as anti-proliferative microRNAs including, miR-126-3p [41– 47], miR-99a-5p [48– 54], miR-125a-5p [55– 59], and miR-139-5p [60– 62]. [score:6]
Our studies confirmed enrichment of microRNAs miR-10b, miR-7f, miR-101, miR-26a, miR-26b, miR-29a, and miR-30 in non-diseased palmar fascia samples. [score:3]
Established anti-fibrotic microRNAs identified in our analysis include let-7 [23– 25], miR-29a-3p [26], miR-26b-5p, miR-30d-5p [28, 29], miR-27b-3p [30, 31], miR-10a-5p [33], miR-26a-5p [37– 40], miR-101-3p [41– 44], miR-27a-3p and miR-10b-5p [45]. [score:1]
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Subsequently, it has been demonstrated that miR-15, miR-16, miR-26, miR-196a-2, and let-7a, which target both the HMGA genes, are drastically downregulated in a panel of 41 human PAs of different histotypes, and their expression is inversely correlated with the HMGA expression. [score:10]
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An additional regulator of MAP3K7 is miR-26b which down-regulates MAP3K7 and inhibits the NF-κB pathway in hepatocellular carcinoma [39]. [score:7]
In agreement, in our initial miRNAs microarray miR-26b was also down-regulated in melanoma cell lines compared to NHEM [15]. [score:3]
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63
[+] score: 10
Other miRNAs from this paper: hsa-mir-185
Another study also indicated that microRNA-miR-26b could inhibit HCC cell migration and invasion via the downregulation of EphA2 [37]. [score:6]
Li H MiR-26b inhibits hepatocellular carcinoma cell proliferation, migration, and invasion by targeting EphA2Int J. Clin. [score:4]
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64
[+] score: 10
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-27a, hsa-mir-30a, hsa-mir-31, hsa-mir-98, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, hsa-mir-192, hsa-mir-197, hsa-mir-199a-1, hsa-mir-208a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-187, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-211, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-144, hsa-mir-145, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-138-1, hsa-mir-146a, hsa-mir-200c, hsa-mir-155, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-375, hsa-mir-328, hsa-mir-337, hsa-mir-338, hsa-mir-339, hsa-mir-384, hsa-mir-424, hsa-mir-429, hsa-mir-449a, hsa-mir-485, hsa-mir-146b, hsa-mir-494, hsa-mir-497, hsa-mir-498, hsa-mir-520a, hsa-mir-518f, hsa-mir-499a, hsa-mir-509-1, hsa-mir-574, hsa-mir-582, hsa-mir-606, hsa-mir-629, hsa-mir-449b, hsa-mir-449c, hsa-mir-509-2, hsa-mir-874, hsa-mir-744, hsa-mir-208b, hsa-mir-509-3, hsa-mir-1246, hsa-mir-1248, hsa-mir-219b, hsa-mir-203b, hsa-mir-499b
Targets of the most remarkably down-regulated miRNAs (let-7, miR-10, miR-26, miR-30, miR-34, miR-99, miR-122, miR-123, miR-124, miR-125, miR-140, miR-145, miR-146, miR-191, miR-192, miR-219, miR-222, and miR-223) regulate proliferation, gene expression, stress response, apoptosis, and angiogenesis. [score:9]
Of most interest are miRNAs: let-7f, let-7i, miR-24, miR-26b, miR-27a, miR-221, miR-30b, miR-337, miR-339-5p, miR-453, miR-520a, miR-574, and miR-744. [score:1]
[1 to 20 of 2 sentences]
65
[+] score: 10
In addition, the in vitro expression of miR-26 in liver cancer cells induced cell-cycle arrest associated with direct targeting of cyclin D2 [64]. [score:6]
MicroRNAs miR-26a and miR-26b have also been found downregulated in distinct types of cancer tissue, including squamous cell carcinoma of the tongue [63]. [score:4]
[1 to 20 of 2 sentences]
66
[+] score: 9
Therefore, it is rational to presume that miR-26b may function together with these four let-7 family members to consistently regress the expression of Lin28B, and dysfunction of their functional cooperation may lead to up-regulation of Lin28B, which in turn contribute to tumorigenesis. [score:6]
The sub-network II is composed of six members of the let-7 family (let-7a, let-7b, let-7c, let-7d, let-7f, and let-7g), the miR-30 family, the miR-195/miR-497 cluster, and two unrelated miRNAs including miR-26b and miR-150. [score:1]
The function of miR-26b is unclear. [score:1]
It is notable that miR-26b is highly connected with four let-7 family members including let-7a, let-7d, let-7f and let-7g. [score:1]
[1 to 20 of 4 sentences]
67
[+] score: 9
Nicotinamide phosphoribosyl transferase (Nampt) is a target of microRNA-26b in colorectal cancer cells. [score:3]
Downstream of Wnt, MYC transcriptionally activates the miR-17-92 locus, but represses expression of miR-15, miR-26 and miR-30. [score:3]
Tumor suppression by miR-26 overrides potential oncogenic activity in intestinal tumorigenesis. [score:3]
[1 to 20 of 3 sentences]
68
[+] score: 9
Dysregulated miRs in breast CAF included upregulation of miR-221, miR-31, and miR-221 with the downregulation of miR205, miR-200b, miR-200c, miR-141, miR-101, miR-342, let-7g and miR-26b affecting all aspects of cell differentiation and paracrine regulation (Zhao et al. 2012). [score:9]
[1 to 20 of 1 sentences]
69
[+] score: 9
For example, overexpression of miR-23a, miR-23b, and miR-24-2 and downregulation of miR-26b are common to GH-secreting and PRL-secreting pituitaries but are not observed in nonfunctioning adenomas [176]. [score:6]
Important cell cycle regulatory proteins such as PTEN and Bmi1 are regulated by miR-26b and miR-128, respectively [168]. [score:3]
[1 to 20 of 2 sentences]
70
[+] score: 9
rno-miR-novel-8, rno-homolog-miR-26, and rno-homolog-miR-199 miRNAs were selected from Tier 1, and rno-miR-sno-57 miRNA was selected from Tier 2. In addition, we analysed the expression of miR-741-3p and miR-743a-3p and found that, in accordance with sequencing data, they were highly expressed in rat PSCs. [score:5]
rno-homolog-miR-26 and rno-homolog-miR-199 miRNAs were expressed in EFs, ESCs and iPSCs, which is consistent with the data obtained from sequencing. [score:3]
Four novel miRNAs with the following coordinates: chrX:−:151288045–151288101 (rno-miR-novel-8); chr7:+:70463555–70463594 (rno-homolog-miR-26); chr3:+:16697111–16697143 (rno-homolog-miR-199); and chr18:−:69422790–69422857 (rno-miR-sno-57) were selected for the validation. [score:1]
[1 to 20 of 3 sentences]
71
[+] score: 8
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-16-1, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-96, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-217, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-27b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-145, hsa-mir-152, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-136, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-193a, hsa-mir-194-1, hsa-mir-320a, hsa-mir-155, hsa-mir-181b-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-34c, hsa-mir-26a-2, hsa-mir-302b, hsa-mir-369, hsa-mir-375, hsa-mir-378a, hsa-mir-328, hsa-mir-335, hsa-mir-133b, hsa-mir-409, hsa-mir-484, hsa-mir-485, hsa-mir-486-1, hsa-mir-490, hsa-mir-495, hsa-mir-193b, hsa-mir-497, hsa-mir-512-1, hsa-mir-512-2, hsa-mir-506, hsa-mir-509-1, hsa-mir-532, hsa-mir-92b, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-33b, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-1224, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-802, hsa-mir-509-2, hsa-mir-509-3, hsa-mir-548e, hsa-mir-548j, hsa-mir-548k, hsa-mir-548l, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-548q, hsa-mir-548s, hsa-mir-378b, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-320e, hsa-mir-548x, hsa-mir-378c, hsa-mir-4262, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-378f, hsa-mir-378g, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-378h, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-378i, hsa-mir-548am, hsa-mir-548an, hsa-mir-203b, hsa-mir-548ao, hsa-mir-548ap, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-378j, hsa-mir-548ay, hsa-mir-548az, hsa-mir-486-2, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
Stringer R. L. Laufer B. I. Kleiber M. L. Singh S. M. Reduced expression of brain cannabinoid receptor 1 (CNR1) is coupled with an increased complementary micro -RNA (miR-26b) in a mouse mo del of fetal alcohol spectrum disorders Clin. [score:3]
Increased miR-26b targets and decreases the levels of cannabinoid receptor 1 (CB [1]R) [149]. [score:3]
Further studies are needed to confirm whether miR-26 plays a role in decreasing CB [1]R levels in the brain of patients with alcoholism or acute alcohol exposure. [score:1]
Prenatal exposure of alcohol results in life-long problems, e. g., a recent study in mice exposed to ethanol before birth showed increased miR-26b in the brain of the next generation of mice. [score:1]
[1 to 20 of 4 sentences]
72
[+] score: 8
In COCs, the expression of miR-23b-3p was set as 1 and the expression levels of other miRNAs were compared with that of miR-26b-5p. [score:4]
In CRCs, the expression of miR-26b-5p was set as 1 and the expression levels of other miRNAs were compared with that of miR-26b-5p. [score:4]
[1 to 20 of 2 sentences]
73
[+] score: 8
The results showed that the expression levels of miR-92a-3p and miR-191-3p were 385 and 4.6 fold higher than the expression level of miR-26b-5p (Figure  2C). [score:5]
These relative abundance ratios were close to the ratios from the sequencing data using the Illumina kit (441 fold for miR-92a-3p versus miR-26b-5p, and 10.7 fold for miR-191-3p versus miR-26b-5p). [score:1]
To validate the RNA sequencing data, we performed a qPCR analysis of miR-92a-3p, miR-191-3p, miR26b-5p, and β-actin. [score:1]
To validate the sequencing data, we selected three miRNAs with different read counts for qPCR quantification; namely, miR-92a-3p, which had a high read count, and miR-191-3p and miR-26b-5p, which had relatively low counts. [score:1]
[1 to 20 of 4 sentences]
74
[+] score: 8
Xie et al. revealed 14 upregulated miRNAs (including miR-21, miR-26b and miR-30b) and 19 downregulated miRNAs (including let-7i, miR-7 and miR-622) which contributes to gastric cancer development and progression by using miRNA microarray profiling [16]. [score:8]
[1 to 20 of 1 sentences]
75
[+] score: 8
Highly expressed microRNAs in the brain include a number of regulators of neuronal development and differentiation such as miR-124a, miR-124b, miR-9, and miR-26 (Table  2) [28– 33]. [score:5]
Highly expressed microRNAs in the skeletal muscle include the muscle specific microRNAs, or myomiRs, miR-1 and miR-133a [37, 38], along with miR-26, miR-125b, and miR-27 all of which are involved in myogenesis and skeletal muscle repair (Table  2) [39– 42]. [score:3]
[1 to 20 of 2 sentences]
76
[+] score: 8
However, Ji and colleagues found that miR-26 was downregulated and was associated with hepatocellular carcinoma via activation of the NF-κB pathway [47]. [score:4]
Indeed, it has been reported that miR-26 is amplified in high-grade glioma and facilitates gliomagenesis through downreregulation of the tumor suppressor PTEN [46]. [score:4]
[1 to 20 of 2 sentences]
77
[+] score: 8
Interestingly, upregulation of several miRNAs (miR-214, miR-26, and miR-29) collaboratively represses PcG complex expression and function in myocytes and thereby promotes muscle-specific gene expression and differentiation (Figure 1). [score:8]
[1 to 20 of 1 sentences]
78
[+] score: 8
The top five downregulated were: miR-26b (1 million-fold), miR-20a (1 million-fold), Let-7f (1 million-fold), miR-22–3p (1 million-fold), and Let-7c (364-fold). [score:4]
The top five downregulated were: miR-20a (1 million-fold), miR-22–3p (1 million-fold), miR-26b (1 million-fold), Let-7f (1 million-fold), and miR-30c (3545-fold). [score:4]
[1 to 20 of 2 sentences]
79
[+] score: 8
In breast cancer, 11 dysregulated miRNAs were identified in CAFs: 3 up-regulated miRNAs, miR-221-5p, miR-31-3p, and miR-221-3p, and 8 down-regulated miRNAs, miR-205, miR-00b, miR-200c, miR-141, miR-101, miR-342-3p, let-7 g, and miR-26b [16]. [score:8]
[1 to 20 of 1 sentences]
80
[+] score: 8
AMPK is a known inhibitor of TGF 40, which was targeted by three miRNAs (miR-26a, miR-26b, and miR-744) that were upregulated by metformin in mouse lung. [score:8]
[1 to 20 of 1 sentences]
81
[+] score: 8
Stringer R. L. Laufer B. I. Kleiber M. L. Singh S. M. Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro -RNA (miR-26b) in a mouse mo del of fetal alcohol spectrum disorders Clin. [score:3]
MicroRNA-26b, which is implicated in the differentiation of NSCs [227], has also been shown to control the expression of genes that encode for brain-derived neurotrophic factor (BDNF), which is important for neurodevelopment [226, 227]. [score:3]
In another study, using P7 mouse mo del of FASD, alcohol was shown to enhance miR-26b levels in adult whole brain tissues [230]. [score:1]
Dill H. Linder B. Fehr A. Fischer U. Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2 Genes Dev. [score:1]
[1 to 20 of 4 sentences]
82
[+] score: 8
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-25, hsa-mir-26a-1, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-92a-1, hsa-mir-93, hsa-mir-98, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-196a-1, hsa-mir-197, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-141, hsa-mir-143, hsa-mir-145, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-146a, hsa-mir-150, hsa-mir-194-1, hsa-mir-206, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-106b, hsa-mir-29c, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-26a-2, hsa-mir-372, hsa-mir-374a, hsa-mir-375, hsa-mir-328, hsa-mir-133b, hsa-mir-20b, hsa-mir-429, hsa-mir-449a, hsa-mir-486-1, hsa-mir-146b, hsa-mir-494, hsa-mir-503, hsa-mir-574, hsa-mir-628, hsa-mir-630, hsa-mir-449b, hsa-mir-449c, hsa-mir-708, hsa-mir-301b, hsa-mir-1827, hsa-mir-486-2
Moreover, it was demonstrated that miR-26 family is under-expressed in the majority of SCLC tumors, wheras its upregulation solws down the cellular proliferation by delaying the cells in the G1 phase and by targeting SLC7A5 [146]. [score:8]
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83
[+] score: 7
Other miRNAs from this paper: hsa-mir-26a-1, hsa-mir-26a-2
Forced expression of miR-26 inhibits the growth of stimulated breast cancer cells and tumor in xenograft mo dels by reducing the mRNA expression levels of AMMECR1 and other genes [70]. [score:7]
[1 to 20 of 1 sentences]
84
[+] score: 7
As reflected by the lower overall correlation values (Table 2), the relative expression of the FFPE9a sample indicated that qPCR -based expression was highly divergent in nine of 37 miRNA transcripts with the other expression platforms (let-7a, miR-125a-5p, miR-31, miR-484, miR-16, miR-455-3p, miR-26b, let-7f, and miR-29b; Table S3b). [score:7]
[1 to 20 of 1 sentences]
85
[+] score: 7
Other miRNAs from this paper: hsa-mir-26a-1, hsa-mir-101-1, hsa-mir-101-2, hsa-mir-26a-2
Given that many previous reports have indicated the direct regulatory role of miRNAs for EZH2 gene, including miR26 and miR101, 31, 32 there is possibility that LDM may regulate these miRNAs to indirectly affect EZH2 gene expression. [score:7]
[1 to 20 of 1 sentences]
86
[+] score: 7
Exposure to RDX also induced aberrant expressions of other onco-miRNAs and tumor-suppressing miRNAs, such as let-7, miR-10b, miR-15, miR-16, miR-26 and miR-181, which regulated tumor pathogenesis or genes related to the cell cycle (e. g., TNKS) [45]. [score:6]
In human airway epithelial cells, diesel exhaust particles (DEP), the largest source of emitted airborne particulate matter (PM), induced miR-513b, miR-513c, miR-923, miR-494 and miR-338, and repressed miR-31*, miR-26b, miR-96, miR-27a, miR-135 and miR-374a. [score:1]
[1 to 20 of 2 sentences]
87
[+] score: 7
In mice, Davidson and colleagues studied the effect of a diet based on corn oil-cellulose compared with a diet based on fish oil (EPA and DHA) and pectin in the presence of carcinogens: their results demonstrated an increased expression of miR-16, miR-19b, miR-21, miR-26b, miR-27b, miR -93, 200c, and miR-203 and the decreased expression of some of their direct targets, such as, PTK2B, TCF4, PDE4B, HDAC4, and IGF1 [158], thus suggesting some different molecular mechanisms involving the fish oil diet. [score:7]
[1 to 20 of 1 sentences]
88
[+] score: 7
miR-26b is down-regulated in the tissue and blood, yet up-regulated in the urine [18, 33]. [score:7]
[1 to 20 of 1 sentences]
89
[+] score: 7
microRNAs downregulated in quiescent cells included miR-18, miR-20, miR-29, and miR-7, and microRNAs upregulated with quiescence included let-7b, miR-125a, miR-30, miR-181, miR-26, and miR-199. [score:7]
[1 to 20 of 1 sentences]
90
[+] score: 7
When considering fold changes, the most upregulated miRNAs were miR-31, miR-100, miR-378a, miR-18a, and miR-584, whereas the most downregulated ones were miR-143, miR-26b, miR-125a, miR-148a, and miR-192 (Fig.   3c). [score:7]
[1 to 20 of 1 sentences]
91
[+] score: 7
MiR126, miR146a, miR34a, and miR493 were published as down-regulated (Lodygin et al., 2008; Saito et al., 2009; Veerla et al., 2009; Ueno et al., 2012), and miR199b and miR26b were published as up-regulated in BC (Gottardo et al., 2007; Veerla et al., 2009). [score:7]
[1 to 20 of 1 sentences]
92
[+] score: 7
It is however interesting to note that several miRNAs in addition to miRNA-210 i. e., miR-23, miR-24, miR-26a, miR-26b, miR-29a and miR-107 up-regulated through time course infection in our study were described as hypoxia-related [77], [78], negatively regulating HIF-1α through factor inhibiting-HIF-1α (FIH) [79] or induced by this TF [80]. [score:7]
[1 to 20 of 1 sentences]
93
[+] score: 7
However, some of the miRNAs found to be upregulated in PBMCs of patients with major depressive disorder (MDD), such as hsa-miRNA-26b and hsa-miRNA-1972 [54] are not upregulated in our cohort of FM patients (GEO datasets GSE65033 (http://www. [score:7]
[1 to 20 of 1 sentences]
94
[+] score: 7
With respect to thyroid cancer, several miRNAs (i. e., miR-220, miR-221, and miR-222) have been shown to be significantly upregulated, while several other miRNAs (i. e., let-7, miR-26, and miR-345) have been shown to be significantly downregulated in papillary thyroid carcinoma (PTC) cells [3– 6]. [score:7]
[1 to 20 of 1 sentences]
95
[+] score: 7
The expression of miRNAs in epithelial cells was similar to that in whole lung and included miR-125a, miR-30b/c/d, miR-20d, miR-93 and miR-26b, although some of the miRNAs were also significantly expressed in macrophages and fibroblasts (e. g. miR-30c). [score:5]
In addition, members of the let-7 family (let-7a, let-7b and let-7c), miR-26 family (miR-26a and miR-26b), miR-125 family (miR-125a and miR-125b) and miR-30 family (miR-30a-5p, miR-30b and miR-30c) also fell within the highly expressed category and are therefore considered to be human airway specific (figure 4). [score:2]
[1 to 20 of 2 sentences]
96
[+] score: 7
The relationship between spontaneous apoptosis and baseline miRNA expression was examined by Pearson correlation analysis, resulting in significant negative correlations for 29 miRNAs, most of them expressed at high levels, including miR-29a-3p, let-7g-5p, miR-29b-3p, let-7f-5p, let-7a-5p, miR-26b-5p, miR-19b-3p, or miR-155-5p, and positive correlations for 9 miRNAs, all of them expressed at low levels, including miR-1246, or miR-638 (S4 Table). [score:7]
[1 to 20 of 1 sentences]
97
[+] score: 7
Similarly, the most highly expressed miRNAs in normal-like/claudin-low cell lines were hsa-miR-22, hsa-miR-532-3p, hsa-miR-125b, hsa-miR-501-5p, and hsa-miR-155*, whereas in basal-like cell lines miRNAs of the miR-200 family (hsa-miR-492, hsa-miR-26b, hsa-miR-617, hsa-miR-155) were highly expressed (fold change ≥ 2) (see Table S9 in Additional file 1). [score:5]
Another group of 17 miRNAs (hsa-miR-575, hsa-miR-155, hsa-miR-26b, hsa-miR-200a, hsa-miR-200b, hsa-miR-141, hsa-miR-200c, hsa-miR-190b, hsa-miR-492, hsa-miR-640, hsa-miR-196a, hsa-miR-29c, hsa-miR-93, hsa-miR-193a-3p, hsa-miR-191, hsa-miR-26a, hsa-miR-182) showed significantly higher expression in the major cluster compared with the other miRNAs (fold change ≥ 1.5) (Figure 2, bottom red box). [score:2]
[1 to 20 of 2 sentences]
98
[+] score: 7
ATP13A3 ATPase 13A3 N/A CDKN1A cyclin dependent kinase inhibitor 1A[33] GSK3B glycogen synthase kinase 3 beta[34] RAPH1 Ras association (RalGDS/AF-6) and pleckstrin homology domains 1 N/A SLC38A1 solute carrier family 38 member 1 N/A TET3 tet methylcytosine dioxygenase 3 N/A TP53INP1 tumor protein p53 inducible nuclear protein 1 N/A TSPAN14 tetraspanin 14 N/A Group C (miR-21, miR-23, miR-26a, miR-26b, miR-93, miR-223). [score:3]
In the control patient network, miR-23, miR-26a and miR-26b are strongly connected each through 11 edges; miR-93 and miR-155 are also strong connected to 10 other nodes through 10 edges. [score:1]
These nodes are represented by miR-26a, miR-26b, miR-23, miR-93 miR-146 and miR-155 for the control group. [score:1]
To better illustrate our findings, we applied the principle of predator-prey like mathematical mo del to our groups of miRNAs, S = {miR-182, miR-146, miR-155, miR-16, miR-29a} and C = {miR-23, miR-26a, miR-26b, miR-93, miR-223, miR-21}. [score:1]
The C group is composed of six miRNAs–miR-23, miR-26a, miR-26b, miR-93, miR-223 and miR-21. [score:1]
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99
[+] score: 7
Recently, Zhao et al showed that a tumor suppressor miRNA miR-26b inhibits cancer growth by targeting TAK1 and TAB3 [31]. [score:7]
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100
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In addition, miR-26b was drastically downregulated in the high aggressive thyroid anaplastic carcinoma, whereas its levels did not change in the papillary and follicular histotypes, less aggressive thyroid carcinoma entities (57). [score:4]
MiR-26 was downregulated in hepatocarcinoma (55) and colorectal carcinoma (56), and its loss was significantly linked to the metastatic phenotype. [score:3]
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