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208 publications mentioning mmu-mir-9b-3 (showing top 100)

Open access articles that are associated with the species Mus musculus and mention the gene name mir-9b-3. 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: 407
Bioinformatic analysis identified putative miR-9 target sites within the 3’-UTR of 40 gene transcripts that were significantly down-regulated with miR-9 overexpression, suggesting that miR-9 may directly target and regulate expression of these candidate genes (Table  3, bolded). [score:14]
Indeed, miR-9 overexpression in normal mast cells resulted in increased expression of CMA1 with a concomitant decrease in the expression of secretory leukocyte peptidase inhibitor (SLPI), a direct inhibitor of chymase [49]. [score:12]
Furthermore, down-regulation of peroxisome proliferator-activated receptor δ (PPARG) was observed in BMMCs following enforced miR-9 expression, a finding consistent with recent studies demonstrating that regulation of PPARG expression is mediated by miR-9 through direct targeting of its 3’-UTR [25]. [score:12]
In contrast, miR-9 is downregulated in human ovarian tumor cells and overexpression of miR-9 suppresses their proliferation, in part by downregulating NFκB1 [40, 42]. [score:11]
Bioinformatic analysis identified putative miR-9 target sites within the 3’-UTR of 15 gene transcripts that were significantly down-regulated following miR-9 overexpression, suggesting that miR-9 may directly regulate these genes (Table  5, bolded). [score:10]
Real-time PCR demonstrated that expression of SERPINF1 and MLANA transcript was up-regulated in P815 cells overexpressing miR-9, whereas CD200R1 and CD200R4 was down-regulated compared to empty vector controls (Figure  6B). [score:10]
To draw firm conclusions regarding direct regulation of target gene expression by miR-9, a functional approach for each gene would be required to validate whether these genes are true miR-9 targets, which although relevant, was outside the scope of this study. [score:9]
In BMMCs overexpressing miR-9, 321 transcripts were significantly up-regulated (>2-fold) and 129 transcripts were significantly down-regulated (Table  3, Table  4). [score:9]
Real time PCR confirmed that one of these genes, peroxisome proliferator-activated receptor δ (PPARG) was down-regulated, a finding consistent with recent studies demonstrating regulation of PPARG by miR-9 through direct targeting of its 3’-UTR [25]. [score:8]
These findings are consistent with the notion that that miR-9 promotes a pattern of gene expression contributing to enhanced invasion and suggests a role for chymase in mediating the biologic functions of miR-9. Interestingly, miR-9 modulated the expression of other proteases in normal mast cells, including up-regulation of heparinase (HSPE). [score:8]
MiR-9 modulated the expression of a large number of gene transcripts, including down-regulation of several putative miR-9 targets identified by computational prediction programs. [score:8]
Consistent with our microarray results, we found that transcripts for HSPE and TLR7 were significantly up-regulated in BMMCs expressing miR-9, whereas transcripts for PPARG, PERP, and SLPI were significantly down-regulated compared to empty vector controls (Figure  6A). [score:8]
Furthermore, enforced miR-9 expression in murine mastocytoma cell lines and normal murine BMMCs with low basal levels of miR-9 enhanced invasion and induced the expression of several target genes associated with metastasis, including chymase (CMA1) and heparinase (HSPE). [score:7]
Furthermore, overexpression of miR-9 is associated with aggressive biologic behavior of canine MCTs, possibly through the promotion of a metastatic phenotype as demonstrated by enhanced invasive behavior of normal and malignant mast cells and alteration of gene expression profiles associated with cellular invasion in the presence of enforced miR-9 expression. [score:7]
While some studies have shown that miR-9 promotes metastasis formation [33, 36- 39] other contrasting studies suggest that increased expression of miR-9 suppresses metastasis formation [40, 41] and that miR-9 inhibits tumor growth [42]. [score:7]
Overexpression of miR-9 significantly altered gene expression in both BMMCs and P815 cells, however, most gene transcripts affected by miR-9 expression differed between normal and malignant mast cells. [score:7]
Transcriptional profiling of normal mouse BMMCs and P815 cells possessing enforced miR-9 expression demonstrated dysregulation of several genes, including upregulation of CMA1, a protease involved in activation of matrix metalloproteases and extracellular matrix remo deling. [score:7]
In our study, we identified gene transcripts that showed similar changes in expression following miR-9 overexpression in both normal and malignant mast cells and validated several genes demonstrating significant changes in expression (interferon -induced transmembrane protein protein 3, IFITM3; PDZK1 interacting protein 1, PDZK1IP1) or implicated in promoting the metastatic phenotype (mast cell chymase, CMA1). [score:7]
In transformed mouse malignant mast cell lines expressing either wild-type (C57) or activating (P815) KIT mutations and mouse BMMCs, miR-9 overexpression significantly enhanced invasion but had no effect on cell proliferation or apoptosis. [score:6]
Consistent with our microarray results, real-time PCR confirmed that enforced miR-9 expression significantly upregulated CMA1, IFITM3, and PDZK1IP1 transcripts in mouse BMMCs and P815 cells (Figure  6C). [score:6]
Previous studies have demonstrated that miR-9 is overexpressed in CDX2 -negative primary gastric cancers and miR-9 knockdown inhibits proliferation of human gastric cancer cell lines [43]. [score:6]
miR-9 expression is up-regulated in canine malignant mast cell lines. [score:6]
Prediction of miR-9 binding to the 3’-UTR of genes down-regulated by miR-9 was performed with computer-aided algorithms obtained from TargetScan (http://www. [score:6]
The opposing roles of miR-9 in various tissues may be explained by the expression of different mRNA targets in distinct cellular and developmental contexts. [score:6]
To gain insight into possible mechanisms underlying the observed miR-9 -dependent invasive behavior of mast cells, we compared the transcriptional profiles of murine BMMCs overexpressing miR-9 to those expressing empty vector and found marked changes in gene expression (Figure  5). [score:6]
Furthermore, miR-9 expression correlates with tumor grade and metastatic status in human breast cancer, providing further support for the idea that altered miR-9 expression may be an important regulator of aggressive biological behavior in MCTs (33). [score:6]
Transcriptional profiling of cells overexpressing miR-9 was performed using Affymetrix GeneChip Mouse Gene 2.0 ST arrays and real-time PCR was performed to validate changes in mRNA expression. [score:5]
We identified 7 gene transcripts (IFITM3, PDZK1IP1, CMA1, MGL1, TMEM223, SLAMF1, CLEC4E) that showed similar changes in expression following miR-9 overexpression in both BMMCs and P815 cells. [score:5]
We performed real-time PCR to validate changes in gene expression for several transcripts altered by miR-9 overexpression, including mast cell chymase (CMA1), interferon -induced transmembrane protein 3 (IFITM3), and PDZK1 interacting protein 1 (PDZK1IP1). [score:5]
Real-time PCR was performed to validate changes in mRNA expression for selected genes affected by miR-9 over expression. [score:5]
We performed real-time PCR to validate changes in gene expression for several transcripts altered by miR-9 overexpression in BMMCs. [score:5]
Our data show that normal mast cells overexpressing miR-9 exhibit markedly increased HSPE expression, supporting the assertion that miR-9 may promote the metastatic phenotype by enhancing the proteolytic activity of a number of proteases important in physical remo deling of the extracellular matrix and activate mediators responsible for cell dissemination. [score:5]
The differences in the biology of these diseases may account for the observed differences in miR-9 expression in canine and murine cell lines. [score:5]
To investigate the functional consequences of miR-9 overexpression in malignant mast cell lines, we stably expressed miR-9 in the mouse P815 and C57 cell lines that exhibit low basal levels of this miRNA using an empty or pre-miR-9-3 expressing lentivirus vector. [score:5]
These data suggest that miR-9 overexpression may contribute to the invasive phenotype of malignant mast cells thereby providing a potentially novel pathway for therapeutic intervention in malignant mast cell disease. [score:5]
Hierarchical clustering was performed for 450 genes differentially expressed (p < 0.05) in mBMMCs expressing either empty vector (EV) or miR-9 (miR9) as determined by one-way ANOVA comparison test (p < 0.05). [score:5]
Furthermore, we found that miR-9 expression was significantly upregulated in aggressive MCTs compared to benign MCTs. [score:5]
Real-time PCR was performed to validate changes in gene expression for transcripts (HSPE, TLR7, PERP, PPARG, SLPI) altered by miR-9 overexpression in mBMMCs (*p < 0.05). [score:5]
Figure 5 Overexpression of miR-9 in normal mouse bone marrow-derived mast cells significantly alters gene expression. [score:5]
Real-time PCR was performed to independently validate expression levels of genes (SERPINF1, MLANA, CD200R1, CD200R4) altered by enforced miR-9 expression in P815 cells (*p < 0.05). [score:5]
Our data demonstrate that overexpression of miR-9 in the C57 and P815 mouse malignant mast cell lines and normal mouse BMMCs significantly enhanced the invasive behavior of mast cells and indicate that miR-9 induces a pattern of gene dysfunction associated with an invasive phenotype regardless of KIT mutation status. [score:4]
As shown in Figure  3B, enforced expression of miR-9 in C57 and P815 mast cell lines significantly enhanced their invasion compared to cells expressing empty vector. [score:4]
These findings provide further support for the notion that miR-9 induces alterations in gene expression that may contribute to the development of an invasive phenotype. [score:4]
Our data demonstrate that unique miRNA expression profiles correlate with the biological behavior of primary canine MCTs and that miR-9 expression is increased in biologically high grade canine MCTs and malignant cell lines compared to biologically low grade tumors and normal canine BMMCs. [score:4]
More recently, miR-9 expression was found to be significantly increased in paired primary tumors and distant metastatic sites, suggesting direct involvement of miR-9 in the metastatic process [34, 35]. [score:4]
We found that unique miRNA expression profiles correlate with the biological behavior of primary canine MCTs and that miR-9 was significantly overexpressed in aggressive MCTs compared to benign MCTs. [score:4]
Figure 6 Identification of transcripts dysregulated by miR-9 overexpression in normal murine BMMCs and P815 malignant mast cells. [score:4]
Consistent with findings in the P815 and C57 cell lines, enforced expression of miR-9 in mouse BMMCs significantly enhanced their invasive capacity compared to cells expressing empty vector (Figure  4B). [score:4]
Mouse mast cell lines and BMMCs were transduced with empty or pre-miR-9 expressing lentiviral constructs and cell proliferation, caspase 3/7 activity, and invasion were assessed. [score:3]
Given the role of chymase in the activation of matrix metalloproteases and extracellular matrix degradation, our findings suggest that miR-9 enhances invasion, in part, through increased expression chymase. [score:3]
A comparison of the transcriptional profiles both from normal BMMCs and malignant P815 cells overexpressing miR-9 found that most gene transcripts altered by miR-9 were specific to normal or malignant mast cells. [score:3]
In our studies, miR-9 expression in mast cell lines did not provide a survival advantage or prevent apoptosis, but it did alter the invasive phenotype, supporting the contextual nature of miR-9 induced effects. [score:3]
Low miR-9 expression in P815 cells may reflect the fact that these cells represent a true leukemia, in contrast to the BR and C2 cell lines which are derived from cutaneous tumors that would metastasize via the lymphatic system. [score:3]
miR-9 expression enhances invasion in normal mouse BMMCs. [score:3]
Taken together, these findings suggest a correlation between miR-9 expression levels in primary canine MCTs and metastatic behavior. [score:3]
miR-9 is overexpressed in biologically high-grade canine MCTs. [score:3]
Interestingly, one of the primary tumor samples collected from a dog with a biologically low-grade MCT expressed high levels of miR-9 and the unsupervised hierarchial clustering of all 24 MCTs demonstrated that this dog’s tumor clustered with the biologically high-grade tumors (Figure  1). [score:3]
FACS -mediated cell sorting based on GFP expression was performed 72 hours post-transduction and miR-9 expression was evaluated by real-time PCR (Applied Biosystems). [score:3]
Furthermore, inhibition of miR-9 in canine mast cell lines would provide further convincing evidence of its importance in mast cell invasion. [score:3]
Following transduction, GFP + cells were sorted and miR-9 expression was confirmed by real-time PCR (Figure  3A). [score:3]
Figure 3 Overexpression of miR-9 enhances invasion of malignant mast cells and has no effect on cell proliferation or apoptosis. [score:3]
To investigate whether overexpression of miR-9 in malignant mast cells affected their capacity to proliferate or survive, mouse C57 and P815 cell lines expressing pre-miR-9-3 lentivirus or empty vector control were cultured for 24, 48, and 72 hrs and the impact on cell proliferation and apoptosis was assessed. [score:3]
Given the potential link between miR-9 expression and biological behavior of MCTs, we next evaluated miR-9 expression in canine (BR and C2) and murine (C57 and P815) mast cell lines and normal canine and murine BMMCs by real-time PCR. [score:3]
To assess the effect of ectopic miR-9 expression on the invasive capacity the BMMCs, a was again performed. [score:3]
Overexpression of pre-miR-9 enhances invasion of malignant mast cell lines. [score:3]
Figure 4 Overexpression of miR-9 enhances invasion in normal mouse bone marrow-derived mast cells. [score:3]
To assess the effect of miR-9 expression on invasion, cell culture inserts (8-μm pore size; Falcon) were coated with 100 μL of Matrigel (BD Bioscience, San Jose, CA, USA) to form a thin continuous layer and allowed to solidify at 37°C for 1 hour. [score:3]
MiR-9 levels were assessed by real-time PCR in wild-type, empty vector, and miR-9 expressing cells (*p < 0.05). [score:3]
Future work to dissect the exact mechanisms through which miR-9 exerts the invasive phenotype is ongoing with the ultimate goal of identifying potential druggable targets for therapeutic intervention. [score:3]
Given prior work from our laboratory showing that the C2 line exhibits invasive behavior in vitro while the P815 line does not [24], it was possible that miR-9 expression was associated with the invasive behavior of mast cells. [score:3]
Furthermore, dysregulation of miR-9 is associated with MCT metastasis potentially through the induction of an invasive phenotype, identifying a potentially novel pathway for therapeutic intervention. [score:2]
MiR-9 overexpression in transformed BMMCs was confirmed by quantitative real-time PCR (Figure  4A). [score:2]
This finding was confirmed by real-time PCR in which a 3.2-fold increase in miR-9 expression was identified in biologically aggressive MCTs as compared to benign MCTs (Figure  2A). [score:2]
Mature miR-9 expression was performed using Taqman miRNA assays (Applied Biosystems). [score:2]
Taken together, these data support the notion that dysregulation of miR-9 may contribute to the aggressive biologic behavior of some canine MCTs. [score:2]
As shown in Figure  2B, canine mastocytoma cells exhibited higher levels of miR-9 expression when compared with normal canine BMMCs. [score:2]
No effects of miR-9 on proliferation or apoptosis were observed in either cell line when compared to cells expressing empty vector (Figure  3C and D). [score:2]
In concordance with the potential role of miR-9 in malignant mast cell behavior, the BR and C2 canine malignant cell lines expressed high levels of miR-9 compared to normal canine BMMCs. [score:2]
Figure 2 MiR-9 is highly expressed in biologically high grade canine MCTs and malignant mast cell lines. [score:2]
These observed differences likely reflect variations in the impact of miR-9 that are dependent on cellular context. [score:1]
miR-9 has no effect on cell proliferation or caspase-3,7 dependent apoptosis in malignant mast cells. [score:1]
In contrast, both mouse C57 and P815 cells and mouse BMMCs demonstrated low basal levels of miR-9. The mouse P815 mastocytoma cell line is a leukemia of mast cell origin, whereas the canine BR and C2 mastocytoma cells are derived from cutaneous tumors. [score:1]
We evaluated the miRNA expression profiles from biologically low-grade and biologically high-grade primary canine MCTs using real-time PCR -based TaqMan Low Density miRNA Arrays and performed real-time PCR to evaluate miR-9 expression in primary canine MCTs, malignant mast cell lines, and normal bone marrow-derived mast cells (BMMCs). [score:1]
To gain insight into possible mechanisms underlying the observed miR-9 -dependent invasive behavior of mast cells, we evaluated the effects of miR-9 expression on the transcriptional profiles of BMMCs and P815 cells. [score:1]
As such, identifying proteins altered by miR-9 that promote cell invasion and validating these targets in canine cell lines/tumors represents an area of ongoing investigation. [score:1]
To characterize the biological consequences of miR-9 overexpression in normal mast cells, we transduced murine BMMCs with pre-miR-9-3 lentivirus or empty control vector. [score:1]
Microarray analysis identified genes affected by miR-9. Discussion. [score:1]
Together, these data suggest that miR-9 promotes an invasive phenotype in mast cells. [score:1]
Interestingly, miR-9 was identified as a pro-metastatic miRNA in human breast cancer cell lines through its ability to enhance cell motility and invasiveness in vitro and metastasis formation in vivo[33]. [score:1]
Transcriptional profiling of cells transduced with miR-9 lentivirus. [score:1]
The present study investigated alterations in gene transcript expression affected by miR-9; however, these changes were not demonstrated at the protein level. [score:1]
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[+] score: 342
Furthermore, both the NF-κB1 mRNA and protein levels were affected by miR-9. Finally, knockdown of NF-κB1 inhibited MGC803 cell growth in a time -dependent manner, while ectopic expression of NF-κB1 could rescue MGC803 cell from growth inhibition caused by miR-9. These findings indicate that miR-9 targets NF-κB1 and regulates gastric cancer cell growth, suggesting that miR-9 shows tumor suppressive activity in human gastric cancer pathogenesis. [score:13]
Finally, in MGC803 cells, suppression of NF-κB1 expression by specific small interfering RNA (siRNA) could also inhibit MGC803 cell growth, while ectopic expression of NF-κB1 could rescue MGC803 cell from growth inhibition caused by miR-9. Nine pairs of gastric samples, including nine human gastric adenocarcinoma tissue samples and nine matched normal gastric tissue samples, were obtained from the Tumor Bank Facility of Tianjin Medical University Cancer Institute and Hospital and the National Foundation of Cancer Research (TBF of TMUCIH & NFCR) with patients' informed consent. [score:11]
Finally, endogenous NF-κB1 expression, both mRNA and protein, is decreased in pri-miR-9 -treated MGC803 cells, suggesting that miR-9 may regulate NF-κB1 protein expression by inducing mRNA degradation and/or translational suppression. [score:10]
It was shown that the amount of NF-κB1 protein was decreased after overexpression of miR-9 (figure 4D), suggesting that miR-9 negatively regulates endogenous NF-κB1 protein expression through translational repression mechanism. [score:8]
Suppression of Gastric Adenocarcinoma Cell Proliferation by Overexpression of miR-9 in vitroTo determine the role of miR-9 in tumor cell proliferation, a miR-9 overexpression vector, pcDNA3/pri-miR-9 (pri-miR-9), was constructed. [score:7]
To determine whether miR-9 suppresses endogenous NF-κB1 through translational repression, MGC803 cells were transfected with pri-miR-9 and the expression of NF-κB1 protein was examined by Western blot. [score:7]
In an EGFP reporter system, overexpression of miR-9 downregulated EGFP intensity, and mutation of the miR-9 binding site abolished the effect of miR-9 on EGFP intensity. [score:7]
These results suggested that NF-κB1 is a direct target of miR-9. Figure 4 NF-κB1 is a direct target of miR-9. (A) The predicted miR-9 binding site on NF-κB1 mRNA 3'UTR is shown. [score:7]
The target genes of miR-9 were predicted using three programs, known as PicTar, TargetScan, and miRBase Targets. [score:7]
These results suggested that NF-κB1 is a direct target of miR-9. Figure 4 NF-κB1 is a direct target of miR-9. (A) The predicted miR-9 binding site on NF-κB1 mRNA 3'UTR is shown. [score:7]
Overexpression of miR-9 Inhibits Xenograft Tumor Growth in vivoTo further determine whether miR-9 is involved in tumorigenesis, we established a stable miR-9-overexpression cell line as well as a control cell line. [score:7]
Experimental evidence indicated that NF-κB1 is a target of miR-9. First, the ability of miR-9 to regulate NF-κB1 expression is likely direct, because it binds to the 3'UTR of NF-κB1 mRNA with complementarity to the miR-9 seed region. [score:7]
In this study, knockdown of NF-κB1 suppressed the growth of MGC803 cells, which was consistent with the results of miR-9 overexpression. [score:6]
Although underexpression of miR-9 in some types of tumors suggested its role in cancer development, the underlying mechanism is still unclear because little is known of miR-9 targets. [score:6]
These results were consistent with the effects of miR-9 overexpression in vitro and strongly suggested that miR-9 could inhibit gastric cancer cell growth. [score:5]
Tumor suppressive miRNAs, such as miR-9, are usually underexpressed in tumors and may fail to control some of the oncogenic genes. [score:5]
The oncogenic role of NF-κB1 in gastric cancer may explain why overexpression of miR-9 can inhibit gastric cancer cell growth. [score:5]
Since miR-9 expression is decreased in cancer tissues, we expected that overexpression of miR-9 would result in the arrest of cell growth. [score:5]
In summary, we show that miR-9 expression is decreased in gastric adenocarcinoma tissues and that pri-miR-9 inhibits gastric cancer cell growth in vitro and in vivo. [score:5]
Ectopic expression of NF-κB1 could also rescue MGC803 cells from growth inhibition caused by miR-9. However, the underlying mechanisms by which NF-κB1 affects gastric cancer cell growth remain to be established. [score:5]
Overexpression of miR-9 Inhibits Xenograft Tumor Growth in vivo. [score:5]
Suppression of Gastric Adenocarcinoma Cell Proliferation by Overexpression of miR-9 in vitro. [score:5]
Overexpression of miR-9 suppressed the growth of human gastric adenocarcinoma cell line MGC803 cell as well as xenograft tumors derived from them in SCID mice. [score:5]
Subsequently, we predicted and confirmed that the tumor-related transcription factor NF-κB1 was a direct target of miR-9 and was negatively regulated by miR-9 at the post-transcriptional level. [score:5]
Hence, the high frequency of aberrant regulation of miR-9 in different types of cancer tissues and cells suggests that downregulation of miR-9 might play an important role in oncogenesis. [score:5]
It was unclear as to how miR-9 affects cell growth and proliferation, because little is known about the physiologic targets of miR-9. Although bioinformatic tools may help to reveal putative mRNA targets of miRNAs, experimental procedures are required for their validation. [score:5]
Figure 2Overexpression of miR-9 suppresses tumor cell growth in vitro. [score:5]
Consistent with this hypothesis, we observed that overexpression of miR-9 inhibited the growth of the gastric adenocarcinoma cell line MGC803 in vitro and in vivo. [score:5]
In this study, we detected differential expression of miR-9 in human gastric adenocarcinoma and adjacent normal tissues through quantitative RT-PCR, and hypothesized miR-9 as a tumor suppressor. [score:5]
Figure 3 Suppression of growth activity of xenograft gastric adenocarcinoma derived from MGC803 cells in SCID mice by overexpression of miR-9. (A) The graphs show the differences between tumor volume in pri-miR-9 group and control group. [score:5]
The validity of miR-9 ectopic expression was confirmed by quantitative RT-PCR, which revealed a 13-fold increase of miR-9 expression in pri-miR-9 -transfected cells than in the control group (figure 2A). [score:5]
Furthermore, the expression of NF-κB1 can be negatively regulated by miR-9. This study extends our knowledge about the regulation of NF-κB1, a tumor-related protein. [score:5]
These data suggested that miR-9 negatively regulate the expression of NF-κB1 through mRNA cleavage mechanism. [score:4]
Interestingly, taking advantage of miRNA expression analysis and real-time TaqMan PCR, it was also found that miR-9 expression was decreased in recurrent ovarian cancer tissues compared to primary cancer tissues [21]. [score:4]
Therefore, identification of miR-9-regulated targets is a necessary step to understand miR-9 functions. [score:4]
Although pri-miR-9 suppressed the EGFP fluorescence intensity of EGFP- NF-κB1 3'UTR, mutation of the miR-9 binding site abolished the effect of miR-9 on the EGFP fluorescent intensity. [score:4]
We showed that miR-9 was downregulated in human gastric adenocarcinoma. [score:4]
To further determine whether miR-9 is involved in tumorigenesis, we established a stable miR-9-overexpression cell line as well as a control cell line. [score:3]
Bioinformatics analysis indicated a putative miR-9 binding site in the 3'-untranslated region (3'UTR) of the tumor-related gene NF-κB1 mRNA. [score:3]
Furthermore, overexpression of miR-9 in MGC803 cells could also decrease the endogenous NF-κB1 mRNA level (figure 4E). [score:3]
At the concentration of 2.5 ng/μl and 15 ng/μl of pri-miR-9 plasmid, cell growth was inhibited by 15% and 45%, respectively (figure 2C). [score:3]
To establish the stable miR-9-overexpression cell line and the control cell line, MGC803 cells were transfected with pcDNA3/pri-miR-9 (pri-miR-9) or pcDNA3 (control), followed by selection for 20-30 days in complete medium supplemented with 800 μg/ml of G418 (Invitrogen). [score:3]
Figure 1 Identification of differential expression of miR-9 in gastric tissues. [score:3]
The stable miR-9-overexpression MGC803 cells or control cells were inoculated with 4 × 10 [6 ]cells per site bilaterally on the axillary fossae of female athymic nude mice aged 6-8 weeks. [score:3]
U6 snRNA was regarded as an endogenous normalizer and the relative miR-9 expression level of the nine pairs of gastric tissues as well as the combined result (mean ± SD) is shown (* P < 0.05). [score:3]
Second, the EGFP fluorescence intensity of EGFP- NF-κB1-UTR was specifically responsive to miR-9 overexpression. [score:3]
The expression level of miR-9 in the nine pairs of gastric adenocarcinoma tissues (Ca) and matched normal tissues (N) was detected by quantitative RT-PCR. [score:3]
In this study, we show that miR-9 targets the NF-κB1 mRNA, thus revealing a potential mechanism associated with gastric tumorigenesis. [score:3]
To determine the role of miR-9 in tumor cell proliferation, a miR-9 overexpression vector, pcDNA3/pri-miR-9 (pri-miR-9), was constructed. [score:3]
Meanwhile, another study provided evidence that miR-9 acts as a tumor suppressor gene in recurrent ovarian cancer [21]. [score:3]
Furthermore, a recent study described aberrant hypermethylation as a mechanism for miRNA genes including miR-9 inactivation and downexpression in human breast cancer [20]. [score:3]
In vivo Tumor Xenograft StudiesTo establish the stable miR-9-overexpression cell line and the control cell line, MGC803 cells were transfected with pcDNA3/pri-miR-9 (pri-miR-9) or pcDNA3 (control), followed by selection for 20-30 days in complete medium supplemented with 800 μg/ml of G418 (Invitrogen). [score:3]
Third, mutation of the miR-9 binding site abolished the effect of miR-9 on the regulation of EGFP fluorescence intensity. [score:3]
Single colonies were picked and amplified, and the expression level of miR-9 was detected by real-time RT-PCR. [score:3]
We discovered that from a total of nine pairs of matched advanced gastric adenocarcinoma tissue samples, the level of miR-9 was downregulated in tumor tissues compared to the matched normal tissues. [score:3]
Moreover, ectopic expression of NF-κB1 could rescue MGC803 cell from growth inhibition caused by miR-9, both in MTT assay (figure 2B) and colony formation assay (figure 2D). [score:3]
We used a three-step consequential approach to identify miR-9 target genes. [score:3]
Quantitative Analysis of miR-9 Expression in Human Gastric Adenocarcinoma. [score:3]
Fourth, we observed an inverse correlation between the expression of miR-9 and NF-κB1 in gastric adenocarcinoma tissues. [score:3]
It was shown that miR-9 expression level was generally and significantly lower in gastric adenocarcinoma tissues than in matched normal gastric tissues (figure 1). [score:3]
Of the predicted target genes, the oncogene NF-κB1, whose mRNA 3'UTR contained a putative binding site of miR-9, was identified. [score:3]
These results indicated that overexpression of miR-9 showed an anti-proliferative effect. [score:3]
The mRNA 3'UTR of candidate miR-9 target gene NF-κB1 carries a putative miR-9 binding site (figure 4A). [score:3]
NF-κB1 is a Candidate Target Gene of miR-9. NF-κB1 Carries a Functional miR-9 Binding Site. [score:3]
Hence, these results indicate that gastric adenocarcinoma cells transfected with pri-miR-9 showed deletion of malignant phenotypes, suggesting a role for miR-9 in the growth suppression of cancer cells. [score:3]
Therefore, we hypothesized that miR-9 is a growth inhibition factor in human gastric adenocarcinoma. [score:3]
The 3'-untranslated region of NF-κB1 mRNA containing the miR-9 binding site was amplified by PCR using the following primers: NF-κB1 sense, 5'-CGC GGATCCTCAACAAAATGCCCCATG-3'; and NF-κB1 antisense, 5'-CG GAATTCAGTTAAATCGAGAATGATTCAGGCG-3'. [score:2]
Several studies on the role of miR-9 deregulation in human oncogenesis have been reported. [score:2]
It may suggest that miR-9 plays important roles in diverse biological processes by regulating NF-κB1. [score:2]
To test the expression of miR-9 in human gastric adenocarcinoma and adjacent normal tissues, real-time RT-PCR assay was performed in nine pairs of gastric tissue samples. [score:2]
In colony formation assay, we observed that the colony formation activity of MGC803 cells transfected with pri-miR-9 was significantly inhibited. [score:2]
To construct the pcDNA3/pri-miR-9 (pri-miR-9) expressing vector, we first amplified a 386-bp DNA fragment carrying pri-miR-9 from genomic DNA using the following PCR primers: miR-9-sense, 5'-CGG AGATCTTTTCTCTCTTCACCCTC-3', and miR-9-antisense, 5'-CAA GAATTCGCCCGAACCAGTGAG-3'. [score:2]
To confirm that this site was responsible for the negative regulation by miR-9, we cloned the putative 3'UTR binding site into the downstream of an enhanced green fluorescence protein (EGFP) reporter gene (EGFP-NF-κB1 3'UTR) and co -transfected this vector with pri-miR-9 or the control vector into MGC803 cells. [score:2]
First, we examined miR-9 expression in gastric adenocarcinoma and matched normal gastric tissues by real-time RT-PCR assay as previously described [24]. [score:2]
To further confirm the effect of miR-9 overexpression on the growth of gastric cancer cells, colony formation assay was performed. [score:2]
Furthermore, we found that the growth rate of tumors derived from MGC803 cells transfected with pri-miR-9 in SCID mice was lower than that of control tumors. [score:1]
MGC803 cells were transfected with pri-miR-9 as well as pcDNA3/NF-κB1 or control vector. [score:1]
As a result, pri-miR-9 had no effect on the intensity of EGFP fluorescence in this 3'UTR mutant vector (figure 4C), highlighting the importance of this miR-9 binding site. [score:1]
MiR-9 Negatively Regulates NF-κB1 at the Post-Transcriptional Level. [score:1]
UTR) reporter vector as well as pri-miR-9 or control vector. [score:1]
MGC803 cells were transfected with pri-miR-9, control vector or pri-miR-9 with pcDNA3/NF-κB1, and then seeded in 12-well plates. [score:1]
When tumors were harvested, the average volume of tumors derived from the pri-miR-9 group was only half of that in the control group (figures 3A & 3C). [score:1]
MGC803 cells were transfected with pri-miR-9 or control vector pcDNA3 in 24-well plates, and then with the reporter vector pcDNA3/EGFP- NF-κB1 3'UTR or pcDNA3/EGFP- NF-κB1 3'UTRmut on the next day. [score:1]
Here, we focused on the role of miR-9 in the pathogenesis of human gastric adenocarcinoma. [score:1]
We also found that the anti-proliferative activity of pri-miR-9 transfection was dose -dependent. [score:1]
Also, four nucleotides at the miR-9 seed sequence binding site of the NF-κB1 3'UTR were deleted using PCR side-directed mutagenesis assay. [score:1]
To detect the dose -dependent effects, we gradually increased concentration of pri-miR-9 from 0 ng/μl to 15 ng/μl. [score:1]
The cDNA was used for the amplification of mature miR-9 and an endogenous control U6 snRNA for all PCR reactions. [score:1]
The cells were transfected with pri-miR-9 or control vector at a final concentration of 5 ng/μl as described above. [score:1]
The colony formation rate of MGC803 cells transfected with pri-miR-9 was significantly lower than the control group (figure 2D). [score:1]
Using the MTT assay, we found that MGC803 cells transfected with the miR-9 overexpression vector (pri-miR-9) exhibited decreased growth compared to control cells. [score:1]
To further determine the function of the miR-9 binding site, we constructed another EGFP reporter vector containing the NF-κB1 3'UTR but with a mutated miR-9 binding site (figure 4B). [score:1]
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Consistent with this, increased apoptosis of articular chondrocytes and PRTG level by DMM surgery was also inhibited with over -expression of miR-9 and stimulated with suppression of miR-9. From previously reported miRNA array data by inhibition of JNK signaling [11], we identified 14 up-regulated miRNAs and 12 down-regulated miRNAs whose expressions were altered during chondrogenesis (Additional file 1). [score:17]
Here, for the first time, we found that PRTG exhibits chondro -inhibitory action in limb mesenchymal cells and that PRTG is a direct target of miR-9. From previously reported miRNA array data by inhibition of JNK signaling [11], we identified 14 up-regulated miRNAs and 12 down-regulated miRNAs whose expressions were altered during chondrogenesis (Additional file 1). [score:16]
Second, the luciferase intensity of PRTG-UTR was specifically responsive to miR-9 over -expression suggesting that miR-9 may regulate PRTG protein expression by inducing translational suppression. [score:10]
As well, inhibited precartilage condensation by JNK inhibition and PRTG over -expression was recovered by co-electroporation of PRTG-specific siRNA or co-introduction of miR-9 (Figure 3D) confirmed its efficiency with PRTG over-expressed cells (Figure 3C lower panel). [score:9]
Target genes of miR-9 were predicted using miRNA target prediction algorithms, including TargetScan and miRDB and PRTG was identified as a potential target. [score:9]
Consistent with this, increased apoptosis of articular chondrocytes and PRTG level by DMM surgery was also inhibited with over -expression of miR-9 and stimulated with suppression of miR-9. During development, most of our bones form through endochondral ossification in which bones are first laid down as cartilage precursor [1] and mitogen-activated protein kinase (MAPK) cascades are known to play essential roles in regulating mesenchymal cell chondrogenesis [2, 3]. [score:9]
Using these cells, we analyzed the changes in the expression of genes and proteins, tested the expression level of miR-9, and applied a target validation system. [score:7]
And chondrocytes isolated from normal human articular cartilage expressed miR-9, and this expression was significantly reduced in OA chondrocytes, especially decreased its expression in parallel with the degree of cartilage degradation. [score:7]
To validate the role of miR-9 in chondrocyte apoptosis during OA cartilage destruction in vivo, we overexpressed miR-9 in cartilage tissue by injecting miR-9 -expressing or si-miR-9 expressing lentiviruses into DMM mouse knee joints (Figure 6E). [score:7]
Experimental evidence indicates that PRTG is a target of miR-9. First, the ability of miR-9 to regulate PRTG expression is likely direct, because it binds to the 3′UTR of PRTG mRNA. [score:7]
And these inhibitory actions of PRTG on precartilage condensation and chondrogenic differentiation were recovered by co-introduction of miR-9. These data suggested that miR-9 suppresses sulfated proteoglycan accumulation and cartilage nodule formation for chondrogenic differentiation possibly by targeting PRTG. [score:7]
To confirm that PRTG is a target for miR-9, we cloned the entire 3′ UTR of PRTG into a luciferase reporter vector, electroporated the vector into chondrogenic progenitors along with the precursor of miR-9 or a cognate non -targeting negative control, and assayed cell lysates for luciferase expression. [score:6]
Figure 2 miR-9 targets PRTG and inhibits chondrogenic differentiation. [score:5]
The RNA level of PRTG was also significantly decreased at 3, 6, and 9 days of culture i. e. at the time of proliferation and condensation with increased expression level of miR-9 and significantly increased at 12, 15, and 18 days of culture, i. e. at the time of hypertrophy and apoptosis with a decreased expression level of miR-9 (Figure 2F). [score:5]
Apoptotic cell death, as assessed by FACS analysis (left panel) and by caspase-3 activity (right panel), was increased by the introduction of PRTG or treatment of JNK inhibitor and inhibited by co-induction of miR-9 (Figure 3C). [score:5]
Apoptotic genes including ABL1, ATP6V1GNOL3, CASP1, 3, 7, CD40, CYLD, and FAS were induced with IL-1β treatments or PRTG over -expression whereas expression levels of those genes were decreased with miR-9 introduction. [score:5]
In support of this prediction, we observed a significant induction in PRTG protein level in miR-9 inhibitor -treated or JNK inhibitor -treated chondroprogenitor cells. [score:5]
Our results revealed that miR-9 inhibitor -induced apoptotic cell death may be responsible for JNK blockade -induced chondro -inhibitory action on precartilage condensation. [score:5]
Among them, miR-9 was one of miRNA whose expression was substantially altered with inhibition of chondrogenic differentiation (determined using a P-value of 0.01 as a cutoff for significance). [score:5]
Our study provides evidence for the mechanism through which miR-9 affects the survival/proliferation of chondrocytes and PRTG is one of the physiologic targets of miR-9 in the regulation of chondrocyte survival. [score:4]
In addition, co-introduction of PRTG or inhibition of miR-9 significantly increased apoptosis in cells treated with TGF-β3 (Figure 4F), a known positive regulator of chondrocytes [27]. [score:4]
In order to examine the involvement of miR-9 during chondrogenesis, we exposed mesenchymal cells to 200 nM peptide nucleic acid -based antisense oligonucleotides (ASOs) against miR-9 (miR-9 inhibitor) whose knockdown efficiency was monitored by real time PCR (Figure 1C, upper panel). [score:4]
Consistent with the results obtained with PRTG over -expression, knock-down of miR-9 promoted the apoptotic death of limb chondroblasts. [score:4]
In sum, here, for the first time, we found that PRTG is regulated by miR-9, resulting in an inhibition of cell proliferation and survival in chondrogenic progenitors and articular chondrocytes. [score:4]
This study shows that PRTG is regulated by miR-9, plays an inhibitory action on survival of chondroblasts and articular chondrocytes during chondrogenesis and OA pathogenesis. [score:4]
MiR-9 is known as a growth inhibition factor and plays a role as in anti-proliferative activity in human gastric adenocarcinoma cells by negatively targeting NF-κB1 at the post-transcriptional level [35]. [score:4]
Down-regulation of miR-9 by blockade of JNK signaling was confirmed by quantitative RT-PCR (Figure 1B). [score:4]
Most significant degeneration was observed in the combination of IL-1β and PRTG -treated cell or in the combination of IL-1β and miR-9 inhibitor -treated cell. [score:3]
Change in expression level of miR-9 in was analyzed by real-time PCR. [score:3]
Consisted with these observations, the protein level of PRTG was increased by co-treatment of miR-9 inhibitor (Figure 4B) and decreased by co-introduction of miR-9 (Figure 4C). [score:3]
Figure 5 miR-9 and its target, PRTG is involved in chondrocyte apoptosis. [score:3]
Treatment of cells with a miR-9 inhibitor caused a significant decrease in total cell numbers (Figure 1D) with significant increases in apoptotic cell death (Figure 1E) and caspase-3 activity (Figure 1F). [score:3]
Human articular chondrocytes isolated from biopsy normal cartilage were electroporated with Prtg or miR-9 in the absence or presence of IL-1β and expression levels of apoptotic genes were examined and represented as heat-map. [score:3]
To further investigate miR-9 involvement in limb formation, 18 HH stage chick embryos were treated with JNK inhibitor in the absence or presence of miR-9 inhibitors. [score:3]
Studies have shown the roles of miR-9 and its validated target, protogenin (PRTG) in the differentiation of chondroblasts to chondrocyte and in the pathogenesis of osteoarthritis (OA). [score:3]
And increased protein level of PRTG by JNK inhibitor treatment was significantly reduced with co-introduction of miR-9 (Figure 2A). [score:3]
Most severe cartilage destruction was observed with the infection of si-miR-9 expression lentiviruses (MFC score of 3, MTP score of 3). [score:3]
Seed sequences of putative targets for miR-9 (Figure 2B upper panel) were exchanged a purine for a pyrimidine and a pyrimidine to a purine. [score:3]
This malformation was overcome by co-treatment of miR-9 inhibitor (Figure 3E). [score:3]
The expressions of type II collagen (Col II), PRTG, and miR-9 were analyzed by real-time PCR (lower panel). [score:3]
Furthermore, decreased in total cell number by JNK inhibitor or PRTG was reversed by co-introduction of PRTG siRNA or miR-9, respectively (Figure 3B, right panel). [score:3]
We confirmed that IL-1β exposure to cells decreased the expression level of miR-9 (Figure 4A). [score:3]
Our laboratory is currently undergoing study on the relationships between miR-9, PRTG, and MMP-13 to verify whether chondrocyte apoptosis by PRTG, a target for miR-9, is down-stream, up-stream, or independent of MMP-13 induction. [score:3]
However, over -expression of miR-9 significantly reduced cartilage destruction (MFC score of 0, MTP score of 0.5). [score:3]
Mice were killed 8 weeks after DMM surgery or 2 weeks after intraarticular injection (1 × 10 [9] plaque-forming units (PFU)) of miR-9 -expressing lentiviruses (lenti-miR-9) for histological and biochemical analyses. [score:3]
A more significant degenerative phenotype and decreased level of type II collagen were observed in co-treatment of miR-9 inhibitor with IL-1β (Figure 4B) and IL-1β -induced degenerative changes were prevented by co-introduction of miR-9 (Figure 4C). [score:3]
Here, we show that miR-9 targets PRTG, thus revealing a potential mechanism for apoptotic death of limb chondroblasts during endochondral ossification. [score:3]
For further validation for apoptotic involvement of miR-9 and PRTG, normal chondrocytes were introduced with miR-9 in the absence or presence of IL-1β or PRTG and expression levels of genes involved in apoptosis was examined (Figure 5). [score:3]
For miRNA target validation, chondroblasts were electroporated with 200 ng of a firefly luciferase reporter construct, 50 pmol of pre-miR-9 or pre-miR -negative (Ambion). [score:3]
It has been shown that miR-9 is responsible for regulating viability of chondrocytes and reduction of miR-9 was observed in generative chondrocytes and this could be a reason for decreasing cell viability. [score:2]
We found that cells transfected with the PRTG-3′ UTR vector plus miR-9 exhibited significantly less luciferase activity compared to cells that received the vector plus the non -targeting negative control (Figure 2B). [score:2]
MiR-9 induces chondro -inhibitory action during chondrogenic differentiation of chick limb mesenchymal cells. [score:2]
MiR-9 stimulated chondrogenic differentiation by regulating protogenin. [score:1]
A more significant decrease was observed with co-treatment of miR-9 or PRTG (Figure 4D). [score:1]
However, the co-treatment with the miR-9 precursor or PRTG-specific siRNA blocked this apoptotic signaling. [score:1]
Figure 4 miR-9 is also involved in the degeneration of articular chondrocytes. [score:1]
Furthermore, we suggested that miR-9 is one of important players in OA pathogenesis. [score:1]
Reduction of miR-9 induction, which results in increased PRTG levels in OA pathogenesis, may be responsible for chondrocyte apoptosis, a typical hallmark of OA. [score:1]
However, IL-1β -induced degeneration was significantly blocked by co-introduction of miR-9. We also observed that increased apoptotic cell death by IL-1β was blocked by co-introduction of miR-9 (Figure 4E right panel). [score:1]
We hypothesized that miR-9 plays a distinct role in endochondral ossification and OA pathogenesis and the present study was undertaken to identify this role. [score:1]
Induction of miR-9 successfully reduced PRTG protein level in myc-tagged PRTG/pCAGGS vector electroporated cells (Figure 2C). [score:1]
We also performed functional study of miR-9 and PRTG. [score:1]
The expression of mir-9 was measured with real-time PCR (upper panel) and Precartilage condensation was analyzed by PA staining at day 3 and Alcian blue staining at day 5 of culture (lower panel). [score:1]
Here, we found another miRNA, miR-9 involved in JNK -induced chondrogenic differentiation. [score:1]
Decreased intensities of PA at day 3 and Alcian blue staining at day 5 were observed with treatment of anti-miR-9 oligonucleotides (Figure 1C, lower panel). [score:1]
In order to further study the role of miR-9 in survival of chondrocytes, dedifferentiation of articular chondrocytes was induced by IL-1β exposure. [score:1]
Here, we also suggest the involvement of miR-9 in OA pathogenesis as well as chondrogenic differentiation of limb mesenchymal cells. [score:1]
Here, we also found that cell viability was decreased in degenerated rabbit and human articular chondrocytes and miR-9: PRTG interplay is involved in the apoptotic process of IL-1β -induced degeneration. [score:1]
Jones and colleagues (2009) suggest the involvement of miR-9 in OA bone and cartilage by mediating the IL-1β -induced production of TNF-α [36]. [score:1]
The protein and RNA levels of type II collagen and miR-9 were decreased whereas those levels of PRTG were increased as the progression of cartilage damage (Figure 6D). [score:1]
For further investigation of involvement of miR-9 or PRTG, macroscopically normal human cartilage from 10 adult donors from both genders (mean age 37.4 years; age range 20–60 years), without history of joint disease was confirmed that the specimens were histological normal cartilage and used for isolating primary articular chondrocytes. [score:1]
With the progression of chondrogenesis, decreased miR-9 level was observed at the time of numerous apoptotic cell deaths. [score:1]
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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-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-141, mmu-mir-152, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-205, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-214, hsa-mir-200b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-141, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, mmu-mir-200a, 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-96, hsa-mir-200c, mmu-mir-200c, mmu-mir-214, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-200a, hsa-mir-130b, hsa-mir-376a-1, mmu-mir-376a, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-182, dre-mir-183, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, dre-mir-205, dre-mir-214, hsa-mir-429, mmu-mir-429, hsa-mir-450a-1, mmu-mir-450a-1, dre-mir-429a, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-130b, dre-mir-141, dre-mir-152, dre-mir-200a, dre-mir-200b, dre-mir-200c, hsa-mir-450a-2, dre-let-7j, hsa-mir-376a-2, mmu-mir-450a-2, dre-mir-429b, mmu-let-7j, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1
Some of the miR-9 and miR-200-class targets upregulated in the mutant OE (Qk, Foxf2) are mesenchymally-expressed rather than OE-expressed, while other targets were actually downregulated in the absence of Dlx5 (Akap6, Elmod1, Snap25) (Table 1C). [score:15]
We found eight miRs differentially expressed, six down-regulated (miR-9, miR-141, miR-200a, miR-200b, miR-429 and miR-376a) and two up-regulated (miR-450a-5p and miR130b*) in the Dlx5 [−/−] OE (Fig.  1a). [score:9]
In summary, since miR-9 and miR-200-class are down-modulated in the absence of Dlx5, while Foxg1 protein level is up-regulated, and since the 3′ UTR of the Foxg1 mRNA is a predicted target of these miRs, we can infer that the Dlx5-miR-Foxg1 regulation is most likely a direct one. [score:8]
Thus, Dlx5 is likely to regulate the expression of miR-9.3 directly, and the expression of miR-200a/ b/ miR-429 indirectly. [score:8]
To determine whether the forced expression of DLX5 may result in an upregulation of miR-9 and miR-200-class RNAs, SH-SY5Y cells were transfected with myc-tagged wild-type DLX5 or Q178P mutant DLX5 expression vectors, and the relative abundance of miR-9 and miR-200 was quantified by Real-Time qPCR. [score:8]
Two possible explanations: either changes in the abundance of miR-9 and miR-200-class cause changes in the abundance of target RNAs that are too modest to pass the imposed cut-off value, or these miRs preferentially affect translation and not stability of the target mRNAs. [score:7]
For chromatin immunoprecipitation (ChIP) we used the human SHSY-5Y neuroblastoma cells, which express low endogenous levels of Dlx5, miR-9 and miR-200, transfected with 5 μg of DLX5-myc-tag expression vector (from Open-Biosystem) or with the same vector in which the Q178P mutation (Shamseldin et al., 2012) was introduced (BioFab, Rome, sequence verified). [score:6]
A significant enrichment of miR-9 and miR-200-class target sequences was detected in the 3′ UTR of genes up-regulated in the Dlx5 [−/−] OE (Table 1A, B). [score:6]
To downmodulate endogenously expressed miR-9 and miR-200 we used the commercially available Ambion anti-miR inhibitors (Life Technologies). [score:5]
myc-tagged version of either the WT or the Q178P mutant DLX5 were expressed in the SH-SY5Y human neuroblastoma cells, which express DLX5, miR-9 and miR-200 endogenously. [score:5]
We also show that Dlx5 promotes expression of miR-9 and miR-200 class, thereby tends to repress Foxg1 protein translation. [score:5]
• Altered expression of miR-9 and -200 might contribute to the Kallmann disease. [score:5]
miR-9 expression is medio-laterally graded, being most intense in the cortical hem; it contrasts with the Foxg1 expression in a reciprocal gradient. [score:5]
2.9To downmodulate endogenously expressed miR-9 and miR-200 we used the commercially available Ambion anti-miR inhibitors (Life Technologies). [score:5]
miR-9 over -expression in developing forebrain at E11.5 resulted in ectopic Reelin + cells over the cortex beyond the marginal zone, while conversely the inhibition of endogenous miR-9 function caused the regression of Wnt3a positive cortical hem and reduction of Reelin+, p73+ and NeuroD1+ cells (Shibata et al., 2008). [score:5]
The expression of pre -miR-9 induced a 6-fold reduction in Foxg1 protein level, while expression of anti -miR-9 induced a 2-fold increase in Foxg1 level (Fig.  3a,b). [score:5]
•Dlx5 controls the expressions of miR9 and miR-200, which target the Foxg1 mRNA • miR-9 and -200 are needed for olfactory neurons differentiation and axon extension • miR-9 and -200 are required for the genesis and position of GnRH neurons. [score:5]
We observed a reduction of miR-9, miR-141 and miR-429 signal in the Dlx5 [−/−] OE, compared to the WT (Fig.  1c), while hybridization with two positive controls, Sp8 (expressed in the OE) and Sox5 (expressed in chondrogenic condensations), yielded an equivalent positive signal in both genotypes, indicating adequate RNA preservation. [score:4]
Indeed Foxg1 has been experimentally shown to be negatively regulated by miR-9. The mouse miR-9 targets Foxg1 mRNAs for proper generation of Cajal–Retzius neurons in the medial pallium (Shibata et al., 2008). [score:4]
3.3 miR-9 is wi dely expressed in the forebrain and olfactory sensory system of the mouse embryo and has been implicated in neural development (La Torre et al., 2013; Shibata et al., 2011; C. Zhao et al., 2013). [score:4]
Next we intersected the predicted miR-9 and miR-200-class targets with the coding mRNAs found to be differentially expressed in the Dlx5 [−/−] OE compared to the WT (Garaffo et al., 2013). [score:4]
miR-9 is wi dely expressed in the forebrain and olfactory sensory system of the mouse embryo and has been implicated in neural development (La Torre et al., 2013; Shibata et al., 2011; C. Zhao et al., 2013). [score:4]
With these two tools, we predicted the most reliable miR-9 targets, and functionally classified the top scoring ones, to search for significantly enriched categories. [score:3]
The 3′ UTR of tetrapod and zebrafish Foxg1 mRNAs hosts miR-9 and miR-200 target sequences. [score:3]
The results presented here indicate that loss of Dlx5 causes a down-modulation of miR-9 and of miR-200-class, which results in the over -expression of the Foxg1 protein. [score:3]
We also show that miR-9 and miR-200-class target (amongst others) the foxg1 mRNA, through which they likely exert their functions. [score:3]
Here we show that mouse and fish foxg1 mRNA is a target of miR-9 and miR-200 class, both of which are down-modulated in the Dlx5 null embryonic OE. [score:3]
Fig. 2), and Foxg1 mRNA has been proposed as a valid target of miR-9 (Shibata et al., 2008). [score:3]
The sequence of miR-9 and mi-200-class shows a high degree of identity between mouse and zebrafish (95% to 100%), as well as high similarity in their expression territories in early embryos ((Choi et al., 2008; Wienholds et al., 2005) and public databases). [score:3]
To overexpress miR-9 and miR-200 exogenously we used commercially available Ambion pre-miR precursors (Life Technologies). [score:3]
3.6To functionally demonstrate a role of miR-9 and miR-200-class for olfactory development, and the involvement of Foxg1 in this regulation in vivo, the zebrafish mo del was again used. [score:3]
To determine whether miR-9 and miR-200-class play a role in GnRH neuronal differentiation and migration, we used the GnRH3:GFP transgenic zebrafish strain, in which the GFP reporter is expressed under the transcriptional control of a fragment of the z- GnRH3 promoter. [score:3]
Searching for functionally relevant targets of miR-9 and miR-200 clsss in the OE. [score:3]
These results indicate that higher expression of foxg1 has similar effects as Dlx5, miR-9 and - 200 depletions on olfactory differentiation, in vivo. [score:3]
We also determined the level of endogenous Foxg1 mRNA, by Real-Time qPCR, upon expression of pre -miR-9 or anti- miR-9, and observed, respectively, a 2-fold decrease and a 2.5-fold increase in the relative Foxg1 mRNA abundance (data not shown). [score:3]
We raised the hypothesis that, in the absence of Dlx5 and reduced levels of miR-9 and - 200-class, Foxg1 protein level is increased due to higher stability/translation of the Foxg1 mRNA. [score:3]
3.7To determine whether miR-9 and miR-200-class play a role in GnRH neuronal differentiation and migration, we used the GnRH3:GFP transgenic zebrafish strain, in which the GFP reporter is expressed under the transcriptional control of a fragment of the z- GnRH3 promoter. [score:3]
We screened for miR expression in ORNs, comparing wild-type vs Dlx5 mutant tissues, and identified miR-9 and miR 200-class as the molecular link between Dlx5 and Foxg1. [score:3]
For miR-9 we detected only three enriched categories: regulation of cell differentiation, cell junction assembly and neuron development (Suppl. [score:3]
To functionally demonstrate a role of miR-9 and miR-200-class for olfactory development, and the involvement of Foxg1 in this regulation in vivo, the zebrafish mo del was again used. [score:3]
The over -expression of DLX5 induced a 2.5–3 fold increase in the abundance of miR-9 in this system, while the Q178P mutant DLX5 did not (Fig.  2d). [score:3]
The knock-down of miR-9 in zebrafish embryos, via injection of a MO previously shown to be specific and effective (Leucht et al., 2008) (sequence in Suppl. [score:2]
Thus, both miR-9 and miR-200 negatively regulate Foxg1 protein level. [score:2]
Genomic regulation of miR-9 and miR-200 by Dlx5. [score:2]
In this work we define the role of miR-9 and miR-200-class in the development of the olfactory system, with functions ranging from ORN differentiation to axon guidance, glomerulus formation and GnRH neuron migration. [score:2]
Examining olfactory development more thoroughly we now can implicate the miR-9 and miR-200-class networks in a more complex phenotype reminiscent of the Kallmann syndrome (see below). [score:2]
miR-9 and miR-200-class regulate Foxg1. [score:2]
To determine whether miR-9 and miR-200-class may modulate Foxg1 protein level, the effect of introduction of pre-miR-9 or depletion of endogenous miR-9 on Foxg1 protein level was assayed by Western blot analysis in SH-SY5Y cells, which express DLX5, miR-9, miR-200-class and Foxg1 endogenously. [score:2]
We injected anti- miR-9 and anti- miR200 (or control) MOs in WT zygotes, then at 48 hpf we extracted total -RNA from these and carried out Real-Time qPCR analyses. [score:1]
3.2The three loci miR-9.1, -9.2 and - 9.3, located on chromosomes 3, 13 and 17 respectively, generate identical mature miR when transcribed, referred to as “ miR-9”. [score:1]
Depletion of miR-9 and miR-200-class in zebrafish results in delayed ORN differentiation. [score:1]
The most altered miR was miR-9, with a fold change of -2, while the other miRs showed a fold-change between − 1.9 and + 1.3. [score:1]
Depletion of miR-9 and miR-200-class in zebrafish results in altered GnRH neuron genesis and position. [score:1]
Table III), led to a significant and dose -dependent reduction of the endogenous miR-9, relative to control -injected ones, accompanied by a 3.5-fold increase of the endogenous z- foxg1 mRNA (Fig.  5d, e). [score:1]
z-foxg1 mRNA level increased by three-folds when either miR-9 or miR-200-class were depleted (Figs.  5e and 6f). [score:1]
3.4The 3′ UTR of the mammalian and fish Foxg1 mRNA contains seed sequences for miR-9 and miR-200 (Suppl. [score:1]
Hybridization was carried out with DIG -labelled riboprobes that specifically detect the mature form of mouse miR-9 and miR-141 (Exiqon) in according with manufactory instruction. [score:1]
Thus, our results provide the first evidence of the participation of miR-9 and miR-200-class in these early events. [score:1]
As a further confirmation, we carried out in situ hybridization on sections of WT and Dlx5 [−/−] embryonic OE, at the age E12.5, to detect miR-9, miR-141 and miR-429, using specific mouse DIG -labelled probes. [score:1]
Upon injection of the anti- miR-9 MO, only approximately 45% of the embryos were found to be CFP + (72% in the control injected), and in these we observed a clear reduction of the CFP + signal. [score:1]
In control embryos, we counted an average of 13 (+/− 2) GnRH3::GFP + neurons/embryo at 72 hpf, while in miR-9 and miR-200 MO injected embryos the average number was, respectively, 5 (+/− 1) and 6 (+/− 1) (Suppl. [score:1]
Anti- z-miR-9 MO was designed with the on-line dedicated tool https://oligodesign. [score:1]
Using reporter zebrafish strains to visualize the embryonic olfactory axons (Miyasaka et al., 2005; Sato et al., 2005; Yoshida et al., 2002) or the GnRH + neurons (Abraham et al., 2008, 2009, 2010), we show that miR-9 and miR-200-class play a role in ORN differentiation and axonal organization. [score:1]
To test whether the DLX5 protein physically occupies the Dlx5 sites near the miR-9.3 and miR-200a/ b/ miR-429 loci, Chromatin Immuno-Precipitation (ChIP) analysis on these sites was performed. [score:1]
We previously verified that the depletion of miR-9 and miR-200-class in zebrafish embryos leads to higher level of z-foxg1 mRNA (no Ab efficiently recognizes the z-foxg1 protein). [score:1]
The 3′ UTR of the mammalian and fish Foxg1 mRNA contains seed sequences for miR-9 and miR-200 (Suppl. [score:1]
The majority of anti -miR-9 injected embryos displayed a normal placode organization, a normal pattern of olfactory axon fasciculation, extension and connectivity, and normal glomeruli formation. [score:1]
Starting from profile data obtained from a mouse mo del of Kallmann syndrome, we functionally examined this pathway in zebrafish showing that miR-9 and miR-200-class are required for normal differentiation of the ORNs, for the extension and connectivity of the olfactory axons, and for the migration of the GnRH neurons from the nasal primordium to the forebrain. [score:1]
This possibility is clearly consistent with the results reported by Shibata et al. (2008), in which they show that the depletion of miR-9 resulted in abnormally high levels of Foxg1 proteins, and this caused a delayed differentiation of the Cajal–Retzius neurons in the cortex. [score:1]
We predicted one Dlx5 binding site near the miR-9.2 locus, located about 1.5 kb downstream, three sites near the miR-9.3 locus, located about 4, 5 and 6 kb downstream, and two sites near the miR-200a–200b-429 locus, located about 5 kb upstream (Fig.  2a). [score:1]
The three loci miR-9.1, -9.2 and - 9.3, located on chromosomes 3, 13 and 17 respectively, generate identical mature miR when transcribed, referred to as “ miR-9”. [score:1]
No Dlx5 binding site was predicted within a 50 kb range from the miR-9.1, miR-141, miR-200c and miR-376a loci. [score:1]
We used the same MOs indicated above to deplete miR-9 and miR-200 class in GnRH3::GFP zygotes, and examined the effect on the number and position of the GFP + neurons associated to the terminal nerves, between 36 and 72 hpf. [score:1]
These data indicate that the depletion of miR-9 results in a delayed or absent differentiation of the OMP + type ORN, with only a minimal effect of the Trpc2 + type neurons, and minimal consequences on axon/glomeruli organization. [score:1]
This provides an indication that the differentiation delay observed upon depletion of miR-9 is specific for the olfactory and anterior brain regions. [score:1]
miR-9 and miR-200 mediate the Dlx5-Foxg1 cascade. [score:1]
[1 to 20 of 76 sentences]
5
[+] score: 204
To further investigate the effect of Ost on neurogenesis by upregulation of miR-9 and subsequent inhibition of the Notch signaling pathway, an antisense miR-9 oligonucleotide was used to inhibit expression and function of miR-9. The results indicated the neuronal differentiation rate of miR-9 inhibitor transfection in the APP group was much lower than that in the GFP and APP groups, accompanied by an increase in NICD and Hes 1 expression, while Ost partially reversed the reduction of neuronal differentiation, accompanied by a reduction of NICD and Hes 1 expression. [score:14]
Consistent with this opinion, the results demonstrated that Ost significantly increased miR-9 expression in APP -expressing NSCs (Figures 3A–C), suggesting that Ost may promote APP -expressing NSCs differentiation into neurons via the upregulation of miR-9. The Notch signaling pathway is involved in nervous system development and the regulation of stem cells biological activities. [score:12]
These results suggest that Ost stimulates APP -expressing NSCs differentiate to neurons partly through upregulation of miR-9 and inhibition of the Notch signaling pathway in APP -expressing cells. [score:10]
Ost increases the differentiation of APP -expressing NSCs into neurons by upregulating miR-9. Ost increases the differentiation of APP -expressing NSCs into neurons by inhibiting the notch signaling pathway. [score:10]
Ost stimulated APP -expressing NSCs to differentiate into more neurons by upregulating miR-9 and inhibiting the Notch signaling pathway. [score:8]
However, Ost may promote NSCs differentiation into neurons via upregulation of miR-9 and subsequent inhibition of the Notch signaling pathway in APP -expressing cells. [score:8]
Consequently, we hypothesized that Ost might improve the differentiation efficiency of APP -expressing NSCs by upregulating miR-9 and inhibiting the Notch signaling pathway. [score:8]
Ost also increases the differentiation of APP -expressing NSCs into neurons through upregulation of miR-9 and inhibition of the Notch signaling pathway. [score:8]
As shown in Figure 4D, miR-9 inhibitor significantly reduced the expression of miR-9, and neuronal differentiation was significantly decreased in the APP plus miR-9 inhibitor group (n = 3, P < 0.01, Figures 4A–C). [score:7]
The results indicated that Ost significantly upregulated miR-9 expression in the DG and CA3 regions (n = 8, P < 0.01, Figure 8), which was consistent with the in vitro result. [score:6]
Neuroprotective effect of osthole on neuron synapses in an Alzheimer's disease cell mo del via upregulation of microRNA-9. J. Mol. [score:6]
In a previous study, we demonstrated that Ost exert a functional protective role in the neuronal synapse through upregulation of miR-9 in APP -overexpressing neural cells (Li et al., 2016). [score:6]
Chang et al. showed miR-9 overexpression attenuates Aβ [42] -induced synaptotoxicity by targeting CAMKK2 (Chang et al., 2014). [score:5]
Subsequently, cells were divided into five groups: GFP (transduced with GFP), APP (transduced with APP), APP+Ost, APP+miR-9 inhibitor, APP+miR-9 inhibitor+Ost. [score:5]
In the present study, APP transduction led to the inhibition of miR-9 expression in these cells (0.57 ± 0.03 in the APP group vs. [score:5]
Quiet a few miRNAs, including miR-9, are specifically expressed in the neurogenic regions of the brain during neural development and in adulthood (Coolen et al., 2013; Meza-Sosa et al., 2014). [score:4]
Ost upregulated miR-9 in APP/PS1 double Tg mice. [score:4]
MicroRNA-9 modulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. [score:4]
The results showed that the number of DG and CA3 neurons as well as the concentration of synaptic proteins in the Tg group sharply decreased, while Ost treatment increased the number of neurons and the concentration of synaptic proteins in Tg mice, partly through upregulation of miR-9. In conclusion, this collective evidence clearly demonstrated that Ost promotes cell survival and reduces cell apoptosis in NSCs by APP transduction. [score:4]
By contrast, Ost treatment resulted in the upregulation of miR-9 (0.90 ± 0.03 APP+Ost group vs. [score:4]
To investigate whether Ost treatment could regulate the expression of miR-9 in APP -expressing cells, a miRNA qRT-PCR assay was used. [score:3]
APP -expressing NSCs were transfected with antisense miR-9 oligonucleotide (GenePharma, Shanghai, China) using Lipofectamine 2000 reagent according to the manufacturer's instructions (Wang et al., 2011). [score:3]
Treatment with Ost partially increased the percentage of NF-M positive cells in the APP plus miR-9 inhibitor group (24.3 ± 1.98% vs. [score:3]
Moreover, APP induces glial differentiation of NPCs through Notch signaling and the basic helix-loop-helix transcription factor Hes 1(Kwak et al., 2011), the target site of miR-9 (Jing et al., 2011). [score:3]
An increasing number of reports have indicated that miR-9 promotes neural differentiation of MSCs and NSCs by targeting Hes 1, STAT3, Zfp521, FoxG, or 1BAF53a (Krichevsky et al., 2006; Shibata et al., 2008; Yoo et al., 2009; Bonev et al., 2012; Rui et al., 2012). [score:3]
Figure 5Effects of osthole and miR-9 on the Notch signaling pathway expression. [score:3]
Figure 8Ost treatment increased miR-9 expression in APP/PS1 Tg mice. [score:3]
the APP plus miR-9 inhibitor group. [score:3]
miR-9 inhibitor transfection and cell differentiation into neurons. [score:3]
miR-9 inhibitor: 5′-UCAUACAGCUAGAUAACCAAAGA-3′. [score:3]
However, notably, miR-9 expression was reduced in both neurons after Aβ treatment and in the brains of AD patients (Schonrock et al., 2010a), and a host of observations showed that miR-9 could be used as a strategy to improve AD. [score:3]
microRNA-9 attenuates amyloidbeta -induced synaptotoxicity by targeting calcium/calmodulin -dependent protein kinase kinase 2. Mol. [score:3]
Moreover, the existence of miR-9 can retard the generation of Tau in the early stages of AD by inhibiting SIRT1 (Charlotte et al., 2012). [score:3]
Some interesting articles have indicated that miR-9 promotes the differentiation of stem cells into neurons by the Notch signaling pathway, as Notch 1 and hes1 are the target genes of miR-9 (Jing et al., 2011; Tan et al., 2012). [score:3]
MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain. [score:3]
Figure 4Ost promotes neuronal differentiation via increasing miR-9 in APP -expressing NSCs. [score:3]
These observations confirmed that the promotion of neuronal differentiation by Ost is attributed to an increase in miR-9 expression. [score:3]
Inhibition of miR-9 led to increased levels of endogenous Hes 1 mRNA and NICD, Hes 1 proteins compared with the GFP group (P < 0.01, Figure 5), while treatment with Ost significantly reduced the levels of endogenous protein compared with the APP plus miR-9 inhibitor group (n = 3, P < 0.05). [score:3]
MiR-9 promotes the neural differentiation of mouse bone marrow mesenchymal stem cells via targeting zinc finger protein 521. [score:2]
miR-9: a versatile regulator of neurogenesis. [score:2]
A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. [score:2]
miR-9 and U6 small nucleolar RNA (Guangzhou RiboBio Co. [score:1]
To further investigate the role of miR-9 in the present study, we used an antisense miR-9 oligonucleotide to inhibit miR-9 (Wang et al., 2011). [score:1]
Thus, we proposed that there is a cross-talk between miR-9 and the Notch signaling pathway in AD mo dels. [score:1]
Involvement of miR-9/MCPIP1 axis in PDGF-BB -mediated neurogenesis in neuronal progenitor cells. [score:1]
miR-9 is one of the most enriched miRNAs in the central nervous system of mammals (Landgraf et al., 2007) and induces neurogenesis in varied mo dels (Krichevsky et al., 2006; Zhao et al., 2009; Yang et al., 2013). [score:1]
To investigate the neuroprotective mechanism of Ost in APP/PS1 transgenic mice, qRT-PCR was used to examine miR-9 expression. [score:1]
[1 to 20 of 47 sentences]
6
[+] score: 154
c Pearson’s correlation analysis showed a negative correlation between miR-9 and ANO1 mRNA expression levels in non-CF and CF bronchial epithelial cell lines (P = 0.012) The increase in miR-9 expression in CF cells led us to hypothesize that ANO1 is a direct target of miR-9. We transfected non-CF cells (16HBE14o-) with a miR-9 mimic and verified the transfection efficiency by qRT-PCR and by using a SmartFlare probe (Supplementary Figs.   8 and 9). [score:8]
As miR-9 has multiple targets, miR-9 inhibitors cannot be utilized to prevent specifically ANO1 downregulation. [score:8]
Upregulation of miR-9 correlates with downregulation of ANO1. [score:7]
Fig. 1Correlation of downregulation of ANO1 mRNA and upregulation of miR-9. a miR-9 expression in non-CF (16HBE14o-; n = 5) and CF (CFBE41o-; n = 6) bronchial epithelial cell lines measured by qRT-PCR. [score:7]
CF cells were transfected with LNA-enhanced oligonucleotides targeting the miR-9 target site in the ANO1 3′UTR (ANO1 TSB) or with a miRCURY LNA microRNA inhibitor negative control (TSB control) (Exiqon, Denmark) using Interferin (Polyplus, Ozyme, France). [score:7]
We show that miR-9 is overexpressed in CF cells where it directly regulates ANO1, causing a decrease in its expression and activity. [score:7]
Histograms represent the mean values ± SDs and were compared using Student’s t-test In this study, we demonstrated that miR-9 was overexpressed in CF bronchial epithelial cells and that it directly downregulated ANO1, a CaCC. [score:6]
We validated ANO1 mRNA as a direct target of miR-9 using luciferase assays to demonstrate that the decreased ANO1 expression in CF cells was caused by miR-9 -mediated ANO1 repression. [score:5]
Based on this knowledge, we propose an alternative strategy to correct chloride efflux in CF patients that rely on a target site blocker (TSB) that prevents miR-9 targeting of ANO1. [score:5]
miR-9 overexpression significantly decreased ANO1 mRNA expression by 60% on average (Fig.   2a). [score:5]
Non-CF and CF cells were transfected with a miR-9 mimic (mirVana® miRNA mimic), miR-9 inhibitor (mirVana [®] miRNA inhibitor), or negative control (mirVana™ miRNA Mimic, Negative Control) (Thermo Fischer Scientific, Courtaboeuf, France) using HiPerfect (30 nM; Qiagen, Les Ulis, France) according to the manufacturer’s instructions. [score:5]
Then, we assessed the effects of miR-9 overexpression on ANO1 mRNA and protein expression. [score:5]
Thus, we concluded that miR-9 negatively regulates ANO1 expression in our mo del of non-CF human bronchial epithelial cells. [score:4]
When the same experiment was conducted in CFBE41o- CF cells using an inhibitor of miR-9, we observed a significant increase in luciferase activity in cells transfected with the inhibitor as compared to those transfected with the control, whereas no significant difference was observed with cells harboring the mutated plasmid (Fig.   3b). [score:4]
To test whether miR-9 represses ANO1 expression by binding to the ANO1 3′UTR, 16HBE14o- cells were cotransfected with a miR-9 mimic and a luciferase reporter vector containing WT ANO1 3′UTR (WT-ANO1 3′UTR) or a negative control reporter harboring mutations in the predicted miR-9 -binding sites (3′UTR mut ANO1). [score:4]
miR-9 regulates ANO1 expression and chloride activity. [score:4]
In addition, miR-9 and ANO1 levels of expression were inversely correlated. [score:3]
Cotransfection with miR-9 mimic resulted in a significant 40% reduction of luciferase gene expression from WT-ANO1 3′UTR as compared to 3′UTR mut ANO1 demonstrating direct miR-9-ANO1 interaction in non-CF cells (Fig.   3a). [score:3]
The cells were cotransfected with 30 nM miR-9 mimic, miR-9 inhibitor, or a negative control (Thermo Fischer Scientific, France). [score:3]
Non-CF cells (16HBE14o-) were transfected with a miR-9 mimic (30 nM) or a negative control for 48 h. a ANO1 mRNA expression was analyzed by RT-qPCR and normalized to GAPDH (n = 3). [score:3]
For the luciferase assay, we used an ANO1-3′UTR-pMirTarget luciferase plasmid (Origene Technologies, Rockville, USA) and an ANO1-3′UTR-pMir vector-bearing mutations in the miR-9 seed region (MIMAT0000441). [score:3]
miR-9 specific TSB increases ANO1 expression and chloride activity. [score:3]
We concluded that miR-9 directly regulates ANO1 in CF cells. [score:3]
miR-9 directly regulates ANO1 in bronchial epithelial cells. [score:3]
CF cells transfected with a miR-9 mimic exhibit a significant decrease of luciferase-3′UTR ANO1 activity and non-CF cells transfected with a miR-9 inhibitor exhibit a significant increase (Supplementary Fig.   12a, b). [score:3]
We studied ANO1 regulation by miR-9 in CF cell lines and primary cultures obtained from patients homozygous for CFTR-F508 del, the most frequent CFTR mutation worldwide. [score:3]
Additionally, we confirmed the specificity of the miR-9 mimic by quantifying the expression of other miRNAs (including miR-19a) by qRT-PCR (Supplementary Fig.   10). [score:3]
Four miRNAs were predicted to target ANO1: miR-9, miR-19a, miR-19b, and miR-144. [score:3]
b Relative luciferase activity in CF cells (CFBE41o-) transiently transfected with luciferase-3′UTR ANO1 or luciferase-3′UTR ANO1 mutated at miR-9 -binding sites and cotransfected with an inhibitor of miR-9 (inh miR-9) or a negative control (control). [score:3]
Because we had previously demonstrated that ANO1 is involved in CF and non-CF cell migration [14], we studied the effect of miR-9 overexpression on 16HBE14o- migration. [score:3]
In conclusion, to our knowledge, the current study is the first to propose a realistic alternative therapy for CF that allows to precisely correct an alternative chloride channel, and the first to report a restoration of the chloride efflux, mucus clearance, and cell migration in a CF context by using a TSB targeting the seed region of miR-9 at the ANO1 3′UTR. [score:3]
miR-9 expression was studied in CF (CFBE41o-) and non-CF (16HBE14o-) bronchial epithelial cells by qRT-PCR and showed a 2.5-fold increase in CF cells as compared to non-CF cells (Fig.   1a). [score:2]
These results suggest that miR-9 regulates ANO1 chloride activity and cell migration in non-CF human bronchial epithelial cells. [score:2]
However, the mechanisms underlying miR-9 deregulation in CF remain currently unknown. [score:2]
Therefore, we investigated the role of miRNAs, especially, miR-9, on ANO1 expression in bronchial epithelial cell lines and primary highly differentiated cells cultured in an air–liquid interface. [score:1]
Interestingly, ANO1 and miR-9 transcript levels were significantly inversely correlated in our cell line mo dels (P = 0.012; Pearson’s correlation) (Fig.   1c). [score:1]
indicated that the ANO1 protein level significantly decreased after transfection of the cells with a miR-9 mimic (Fig.   2b). [score:1]
d Representative images were taken during 4 h of wound closure of non-CF cells transfected with a miR-9 mimic or a negative control (left) and quantification of the migration rates during repair (n = 5). [score:1]
a Relative luciferase activity in non-CF cells (16HBE14o-) transiently transfected with a luciferase-3′UTR ANO1 vector or a luciferase-3′UTR ANO1 vector mutated at miR-9 -binding sites and co -transfected with a miR-9 mimic or a negative control (control). [score:1]
Representative and original traces of ANO1 chloride activity (left) and quantification (right) of non-CF cells transfected with a miR-9 mimic or negative control (n = 8, in triplicates). [score:1]
org) provided information on miR-9 (MI0000466). [score:1]
Non-CF cells were transfected with a miR-9 mimic or a negative control. [score:1]
Thus, we designed a specific TSB that binds to the ANO1 3′UTR (ANO1 TSB) to prevent miR-9 binding. [score:1]
For relative quantification, the ANO1 mRNA level, calculated using the 2 [−ΔΔCt] method, was normalized to the GAPDH mRNA level, and the expression levels of non-CF mo dels and miR-9 were normalized to the RNU6B mRNA level. [score:1]
After 24 h, the cells were transfected with a miR-9 mimic, negative control (Life Technologies, Saint Aubin, France), or ANO1 TSB/LNA control (Exiqon). [score:1]
In addition, we developed an ANO1 TSB that specifically prevents binding of miR-9 to the 3′UTR of ANO1 mRNA, which we previously showed to be decreased in CF [14]. [score:1]
[1 to 20 of 46 sentences]
7
[+] score: 108
Other miRNAs from this paper: mmu-mir-9-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-9b-2, mmu-mir-9b-1
Some key transcriptional regulators controlling the progenitor state were also identified as direct targets of miR-9 24. miR-9 inhibits Her5 and Her9 to promote neurogenesis in the developing brain in zebrafish, while miR-9 over -expression reduces the proliferation of neural progenitors 23. [score:9]
N-myc can negatively regulate miR-9 expression, and miR-9 may regulate GCP proliferation by negatively regulating the expression of Ccnd2 protein. [score:8]
Loss of N-myc increases miR-9 expression, while restoration of N-myc expression could decrease miR-9 expression to normal levels. [score:7]
miR-9 negatively responds to N-myc expression, and the over -expression of microRNA-9 inhibits the proliferation of cerebellar granule neuron precursors in vivo. [score:7]
N-myc can up-regulate miR-9 to increase cell motility and invasiveness in breast cancer cells 27, but it can also down-regulate miR-9 to enhance proliferation in medulloblastomas 28. [score:7]
miR-9 expression was up-regulated more than 2-fold in the GCPs of tTS mice (Fig. 8A), but was reduced to a normal level at P7.5 in the cerebellar granule neuron precursors of tTS mice treated with DOX since P5 (Fig. 8A). [score:6]
miR-9 inhibits proliferation of cerebellar GCPs in vivoTo study whether miR-9 can regulate the proliferation of cerebellar GCPs, miR-9 or a vehicle over -expression lentiviral vector labelled with EGFP were microinjected into the cerebellum of C57 mice at P4. [score:6]
Our findings demonstrate that miR-9 expression is negatively responsive to N-myc expression. [score:5]
Our findings indicate that over -expression of miR-9 in the cerebellum could inhibit the proliferation of GCPs by arresting the cell cycle. [score:5]
In our study, we demonstrate that miR-9 expression negatively responds to N-myc expression in GCPs. [score:5]
These results suggest that N-myc negatively regulates the expression of miR-9 during postnatal cerebellar development. [score:5]
N-myc negatively regulates the expression of miR-9 in GCPs. [score:4]
However, it remains unclear whether N-myc directly regulates miR-9 in GCPs, for example by repressing miR-9 transcription, or if this effect is indirect through post-transcriptional mechanisms or other factors. [score:4]
To study whether miR-9 can regulate the proliferation of cerebellar GCPs, miR-9 or a vehicle over -expression lentiviral vector labelled with EGFP were microinjected into the cerebellum of C57 mice at P4. [score:4]
miR-9 inhibits proliferation of cerebellar GCPs in vivo. [score:3]
It has been reported that Ccnd2 is a target gene of miR-9 in mice 25 26. [score:3]
White arrows indicate the representative granule cell precursors infected with miR-9 or miR-9 vehicle over -expression lentivirus. [score:3]
It has been reported that N-myc can directly bind to the promoter region of miR-9. However, under different circumstances, N-myc can regulate miR-9 in opposing ways. [score:3]
These results indicate that miR-9 can inhibit the proliferation of GCPs in vivo. [score:3]
The miR-9 over -expression GCPs showed almost no Ki-67 positive signal (30 of 32, 93.75%, p < 0.05) (Fig. 8B–E), while GCPs transfected by the vehicle lentivirus generally showed Ki-67 positive signals (Fig. 8F–I). [score:3]
The miR-9 expression level also showed a significant difference between tTS mice with or without DOX treatment (Fig. 8A). [score:3]
However, the exact role of miR-9 in cerebellar development is unknown. [score:2]
miR-9 is an ancient miRNA with a highly conserved mature sequence. [score:1]
The lentivirus-mmu-miR-9 or control lentivirus (Genechem, Shanghai, China) were injected into the developing cerebellum by a 5-μL capacity syringe (Hamilton, Switzerland) with a 33-gauge needle. [score:1]
Four days after microinjection, the proliferation statuses of the GCPs that were transfected with either miR-9 or the vehicle were examined. [score:1]
[1 to 20 of 25 sentences]
8
[+] score: 97
Thus, of the 17 miRNAs upregulated during mESC differentiation that potentially target SIRT1, miR-9 acts early during differentiation to downregulate SIRT1 expression. [score:11]
Inhibition of miR-9 prevents the downregulation of SIRT1 protein expression during differentiation. [score:8]
These data confirm that miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b target endogenous SIRT1 and downregulate its expression. [score:8]
We consistently observed that miR-9 was the first SIRT1 -targeting miRNA to be upregulated both during differentiation of mESCs into embryoid bodies (Figure 3B) and during the directed differentiation of mESCs into neurons (data not shown). [score:7]
Since activation of SIRT1 in neuronal precursors promotes astrocyte formation over neurogenesis [34], SIRT1 might represent a critical target for miR-9. Another similar example is miR-181, which is transiently upregulated during muscle differentiation [35]. [score:6]
To confirm that miR-9 represses SIRT1 early during mESC differentiation, we tested whether inhibition of miR-9 prevents the downregulation of SIRT1 protein. [score:6]
Inhibition of miR-9 prevents downregulation of SIRT1 during mESC differentiation. [score:6]
Site-directed mutagenesis was performed using a QuikChange II Site-Directed Mutagenesis kit (Stratagene; La Jolla, CA) to mutate base pairs 3-6 in the predicted seed region targeted by miR-181 and miR-9 in the SIRT1 3'-UTR. [score:5]
miR-9 is expressed in the brain, induced during differentiation of neuronal precursors into neurons, and regulates neural lineage differentiation [32]. [score:4]
Likewise, co-transfection of a miR-9 expression vector repressed luciferase activity of pGL3-SIRT1 3'-UTR by 30% but not pGL3-SIRT1 3'-UTR 9mt, a control construct with a mutated miR-9 binding site (Figure 4A, right panel). [score:3]
Thus, miR-181 family members and miR-9 target the 3'-UTR of SIRT1 through the predicted seed sites. [score:3]
miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b target endogenous SIRT1. [score:3]
Overexpression of miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b decreased SIRT1 protein levels in mESCs (Figure 4B). [score:3]
Specifically, SIRT1 expression is repressed by miR-181a and b, miR-9, miR-204, miR-135a, and miR-199b. [score:3]
As expected, miR-9 expression strongly increased during differentiation (Figure 5A). [score:3]
For example, miR-9, a miRNA expressed early during mESC differentiation, participates in neuronal differentiation [32]. [score:3]
With this method, 70-80% of the cells in the embryoid bodies were transfected, and LNA-miR-9 specifically increased SIRT1 protein levels ~two-fold (Figure 5D) qRT-PCR analysis demonstrated a more efficient repression of miR-9 expression in the LNA-miR-9 treated cells (Figure 5E), with minimal change in SIRT1 mRNA levels (Figure 5F). [score:3]
To enhance the fraction of cells transfected, we dissociated d6 embryoid bodies, transfected them with LNA-miR-9 or LNA-SCR, reaggregated the embryoid bodies, and assessed SIRT1 expression at d11. [score:3]
These observations confirmed that miR-9 inhibition increased SIRT1 protein levels. [score:3]
LNA-miR-9 reduced expression of miR-9 by 35% atday 8, but LNA-SCR did not. [score:3]
LNA-miR-9 or a scrambled control (LNA-SCR) was transfected into embryoid bodies at d4 and d7. [score:1]
We used a FITC -labelled locked nucleic acid (LNA)-probe antisense to miR-9 to block miR-9 activity (LNA-miR-9). [score:1]
Importantly, LNA-miR-9, but not LNA-SCR or untransfected controls, specifically prevented the differentiation -associated repression of SIRT1 protein (Figure 5C). [score:1]
[1 to 20 of 23 sentences]
9
[+] score: 65
Based on these observations, we concluded that for the most effective attenuation of LGTV replication in the CNS and to ensure the highest stability of viral genome, targets for two different brain-expressed miRNAs (mir-9 and mir-124) should be expressed simultaneously at two (or more) genome regions. [score:7]
Moreover, the most effective virus suppression in the brain was achieved when these cassettes included targets for 2 heterologous miRNAs (mir-124 and mir-9) broadly expressed in the CNS. [score:7]
To confirm that attenuation of C(mir), E(mir) and 3′(mir) viruses was due to the presence of targets for vertebrate brain-specific mir-124 and/or mir-9 and not due to the presence of targets for tick-specific mir-1 (see Fig. 4A), we compared growth rates in the mouse brain for 3′(1/1/1), 3′(9/9/9) and 3′(124/124/124) viruses carrying of three target copies for homologous mir-1, mir-9, or mir-124 miRNA (see Fig. S4A). [score:6]
This likely indicates that combined expression of targets for two different miRNAs (mir-124 and mir-9) in C(mir) and 3′(mir) results in a stronger virus attenuation in the CNS as compared to the targeting for only mir-124 inserted in the E(mir) genome. [score:6]
There is a possibility that insertion of targets for tick-specific miRNAs (mir-1 and mir-275) in combination with targets for CNS-specific miRNAs (mir-124 and mir-9) might prevent microRNA -induced silencing complex (RISC) -dependent attenuation of LGTV replication in the CNS of vertebrates. [score:5]
To assure concurrent restriction of LGTV neurotropism in vertebrate host and replication in its tick vectors, targets for tick-specific mir-1 and/or mir-275 were inserted in tandem with sequences complementary to CNS-specific mir-124 and/or mir-9 into either dCGR, dE/NS1R, or 3′ NCR and three miRNA -targeted C(mir), E(mir) and 3′(mir) viruses were generated, respectively (Fig. 4A). [score:5]
To generate 3′(mir) clone carrying sequences complementary to tick- and CNS-specific miRNAs (Fig. 4A), a fused mir-1/mir-9 target sequence was inserted at nt position 10, and two copies of mir-124 target were introduced at nt positions 14 and 244 of the 3′ NCR of LGTV clone E5. [score:5]
A translational frame (ORF) was restored by inserting a targeting cassette for mir-9, mir-124, mir-1, and mir-124 miRNAs downstream of 5′ promoter region. [score:5]
This demonstrates that presence of intact target sequences for mir-124 and mir-9 in C(mir), E(mir) and 3′(mir) viruses likely resulted only in a negligible effect on viruses attenuation in ISE6 cells, suggesting that LGTV targeting for CNS-specific miRNAs alone does not result in invertebrate-specific host range restriction. [score:5]
To generate 3′(9/9/9), 3′(124/124/124) and 3′(gf/gf/gf) viruses, three target sequences for mir-1 in 3′(1/1/1) construct were replaced with targets for CNS-specific mir-9 or mir-124, or with sequence corresponding to position 241–260 nts of eGFP coding sequence 37. [score:5]
To verify these results, we constructed viruses carrying of three target copies for homologous mir-1, mir-9, or mir-124 miRNA (Fig. S4A) and found that replication of LGTV containing three targets for CNS-specific mir-124 or mir-9 in the 3′ NCR was indistinguishable (p > 0.5; 2-way ANOVA) as compared to replication of LGTV control virus with three copies of random sequences in ISE6 cells (Fig. S4A,B). [score:4]
For both viruses the sequence containing a single target for mir-9 was the most unstable, regardless of its position in the virus genome. [score:3]
However, growth of 3′(1/1/1) virus was significantly higher (p < 0.0001; 2-way ANOVA) as compared to that of 3′(124/124/124) and 3′(9/9/9), which carry target copies for CNS-specific mir-124 or mir-9 in the 3′ NCR (Fig. S4C). [score:2]
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10
[+] score: 65
We found significantly increased expression of miR-9 in primary motor cortex and brainstem motor nuclei, and significantly down-regulated miR-9 in SVZ and hippocampus. [score:6]
In G93A-SOD1 brainstem motor nuclei and primary motor cortex, miR-9 and miR-124a were significantly up-regulated, miR-125b expression was also increased. [score:6]
Our finding that miR-124a and miR-9 are up-regulated in primary motor cortex and brainstem motor nuclei therefore suggests a compensatory response to motor neuron degeneration in these areas highly affected by the disease process. [score:6]
In the present study we have found that in whole brain and brain regions concerned with neurogenesis (SVZ and hippocampus) and affected by motor neuron degeneration (primary motor cortex and brainstem motor nuclei), altered expression of neural fate miR-124a and miR-9 (but not miR-134), cell cycle-related miR-19a and -19b, astrocyte-related miR-125b and oligodendrocyte -related miR-219 occur in late stage disease (18 weeks). [score:5]
Interestingly, at week 18, expression levels of miR-9 and miR-124a, but not miR-134, were significant lower in G93A-SOD1 whole spinal cord than in Wt-SOD1 spinal cord (p < 0.05 and p < 0.01, respectively), whereas miR-19a and -19b expression levels were significantly higher in ALS than Wt-SOD1 mice (p < 0.01 and p < 0.05, respectively) (Additional file 1: Figure S1). [score:5]
We recently found that the expression of neural (miR-9, miR-124a) and cell cycle-related (miR-19a and -19b) miRNAs was significantly associated with altered neuronal fate of cultured ependymal stem/progenitor cells isolated from spinal cord of ALS mice, and that these alterations became more marked as disease progressed [28], suggesting that these miRNAs are involved in ALS pathogenesis and progression. [score:5]
Expression of miR-9, miR-124a, miR-19a and -19b was significantly increased in G93A-SOD1 whole brain at late stage disease compared to B6. [score:4]
miR-9 also correlated negatively with STAT3 in SVZ and hippocampus: STAT3 levels were slightly increased in these regions while miR-9 was significantly down-regulated, again suggesting compromised neurogenesis in these neurogenic areas. [score:4]
At 8 weeks expression levels of miR-9, miR-124a, miR-19a and -19b did not differ significantly between whole brains of G93A-SOD1, B6. [score:3]
Both miR-124a and miR-9 target STAT3 [42]. [score:3]
The later finding is interesting, since miR-9’s absence in mice causes the premature birth of cortical neurons and suppression of neural precursor proliferation in the ventricular and subventricular zones [45] and this might compromise neuroregeneration in the ALS mouse. [score:3]
In addition, miR-9 was significantly up-regulated in G93A-SOD1 brain compared to week 8 (p < 0.01). [score:3]
miR-9 expression was lower in SVZ and hippocampus, and significantly greater in primary motor cortex and brainstem motor nuclei (p < 0.01) in ALS compared to control (Figure  2A). [score:2]
We next analyzed the expression of miR-9, miR-124a, miR-19a and -19b, miR-125 and miR-219 in manually dissected SVZ, hippocampus, primary motor cortex and brainstem motor nuclei in 18-week-old ALS mice compared to same age controls. [score:2]
In our previous study on cultured ependymal stem/progenitor cells isolated from G93A-SOD1 mouse spinal cord at week 18, miR-9 correlated negatively with STAT3 in neural differentiated cells [28], again suggesting involvement of this miRNA-mRNA pair in the regulation of stem cell signaling pathways. [score:2]
We found a good negative correlation between miR-124a and miR-9 and STAT3 in brainstem motor nuclei, again suggesting that neural precursors are being directed toward a neuronal rather than glial fate in this damaged area. [score:2]
Here we investigated neural miR-9, miR-124a, miR-125b, miR-219, miR-134, and cell cycle-related miR-19a and -19b, in G93A-SOD1 mouse brain in pre-symptomatic and late stage disease. [score:1]
In the present study, we first investigated the expression of miR-9, miR-124a, miR-19a, miR-19b and miR-134 in the whole brain of G93A-SOD1 mice in comparison with that of B6. [score:1]
At week 18, miR-9, miR-124a, miR-19a and -19b levels were significantly higher in G93A-SOD1 than control brains (p < 0.01 both B6. [score:1]
miR-9 – an evolutionarily-conserved brain-enriched miRNA [39] – might play an important role in ALS neurodegeneration. [score:1]
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11
[+] score: 64
In addition mir-29 and mir-9 family member were downregulated and their deregulation was associated with different neurodegenerative diseases, including Huntington, Alzheimer, and Parkinson diseases (Saito and Saito, 2012; Tsutsumi et al., 2014) and demyelination-related diseases (Li and Yao, 2012; Tsutsumi et al., 2014). [score:11]
In particular, miR-9 is down-regulated during oligodendrocyte differentiation and its expression level inversely correlates with the expression of its targets Pmp22. [score:10]
In the spinal cord of SOD1 [G93A] transgenic mice that ubiquitously express the mutant SOD1 gene, the miRNA-9 expression is up-regulated (Zhou et al., 2013). [score:8]
The up-regulation of Pmp22 and Mpz proteins in the spinal cord of MLC/SOD1 [G93A] paralleled that of mRNA expression and supports the evidence that these factors are molecular targets of microRNAs, such as miR-1, miR-9, miR-133, and miR-330, that resulted differently modulated in the spinal cord of MLC/SOD1 [G93A] mice compared to wild type littermates. [score:7]
miRNA-9 expression is upregulated in the spinal cord of [G93A]-SOD1 transgenic mice. [score:6]
The difference in the expression levels of miRNA-9 between the global SOD1 [G93A] and MLC/SOD1 [G93A] mice is likely due to SOD1 [G93A] gene ubiquitously expressed in all tissues, including muscle, motor neurons and glia. [score:5]
In particular, we found down regulation of mir-1, mir-330, mir-29, mir-133, and mir-9 family members, whose dysregulation can have profound effects on neuronal physiology and pathology, including Huntington, Alzheimer, and Parkinson diseases (Saito and Saito, 2012). [score:5]
Recently, some specific miRNAs, such as miR-9, miR-23, and miR-29a, were found to participate in the regulation of oligodendrocyte differentiation and myelin maintenance, as well as in the pathogenesis of demyelination-related diseases. [score:4]
Here we observed that the muscle specific expression of the SOD1 mutant gene induces the deregulation of both mir-9 and 29 together with myelin alteration in the sciatic nerve. [score:4]
Graphs indicate relative expression of (A) mir-133a (B) mir-133b (C) mir-9 (D) mir-29 (E) mir-330 (F) mir-1. White bar refers to wild type (Wt) and black bar to MLC/SOD1 [G93A] (Tg). [score:3]
Interestingly, the functional interaction of miR-9 with Peripheral myelin protein 22 (Pmp22) mRNA has been already demonstrated (Lau et al., 2008). [score:1]
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[+] score: 56
A hypothetical mo del of age -dependent miRNAs regulating LCs development and function is shown in Figure 6. Table 1 miRNAs in aging putative targets function in LC reference miR709↑ RANK LC development and homeostasis↓ 49 IRF8 LC development and homeostasis↓ 29 AhR impair LC maturation 33 miR449↑ TGFβRII LC development and homeostasis↓ 32, 46 RunX3 LC development and homeostasis↓ 30 CSF1R LC development and survival↓ 35 miR9↑ TGFβRII LC development and turnover↓ 32, 46 RunX3 LC development and homeostasis↓ 30 RANK LC development and homeostasis↓ 49 miR10a↓ Gfi1 LC development and homeostasis↓ 28 miR200c↓ C/EBP LC differentiation↓ 31 Langerin LC antigen uptake ↑ 22, 23 Gfi1 LC development and homeostasis↓ 28 miR744↓ TGFβI inhibit LC maturation 32, 46 miR20b↓ RANKL inhibit LC maturation 34 miR205↓ C/EBP LC differentiation↓ 31 The density of LCs in the epidermis is known to decrease with age in mice [21]. [score:19]
A hypothetical mo del of age -dependent miRNAs regulating LCs development and function is shown in Figure 6. Table 1 miRNAs in aging putative targets function in LC reference miR709↑ RANK LC development and homeostasis↓ 49 IRF8 LC development and homeostasis↓ 29 AhR impair LC maturation 33 miR449↑ TGFβRII LC development and homeostasis↓ 32, 46 RunX3 LC development and homeostasis↓ 30 CSF1R LC development and survival↓ 35 miR9↑ TGFβRII LC development and turnover↓ 32, 46 RunX3 LC development and homeostasis↓ 30 RANK LC development and homeostasis↓ 49 miR10a↓ Gfi1 LC development and homeostasis↓ 28 miR200c↓ C/EBP LC differentiation↓ 31 Langerin LC antigen uptake ↑ 22, 23 Gfi1 LC development and homeostasis↓ 28 miR744↓ TGFβI inhibit LC maturation 32, 46 miR20b↓ RANKL inhibit LC maturation 34 miR205↓ C/EBP LC differentiation↓ 31 (A) LCs were isolated using AutoMACS with anti-MHCII-PE and anti-PE microbeadsfollowed by a cell sorter. [score:19]
Thus, upregulated miR-449 and miR-9 in aged LCs could downregulate the TGF-β signaling pathway and block LC development. [score:8]
Based on the miRNAs potentially linked to LCs development and function, we have further confirmed that miR-709, miR-449 and miR-9 were upregualated in aging, while miR-200c and miR-10a were downregulated in aging by using single TaqMan RT-PCR assays (Figure 5 D). [score:4]
Interestingly, RANKL/RANK are putative targets of miR-9 or miR-20. [score:3]
miRNAs miR-449 and miR-9 potentially target TGFβ1, TGFβRI, TGFβRII, RunX3 and C/EBP, which are involved in TGF-β signaling (Figure 6). [score:3]
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[+] score: 56
Interestingly, miR-9 maintained its down-regulation in older mice and miR-409-3p was the only miRNA to be consistently down-regulated in APP23 from a very young age right through to older animals. [score:7]
The down-regulated miRNAs miR-9, miR-30 and miR-20 were all strongly predicted to affect target genes involved in axonal guidance. [score:6]
Over -expression of miR-9 accelerates neuronal differentiation, while its inhibition in the medial pallium of E11.5 mouse embryos results in defective differentiation of Cajal-Retzius cells, the first neurons to populate the embryonic cortex. [score:5]
The overlap between human AD and our in vitro and in vivo AD mo dels indicates that amongst the complex pathology in human AD brain, down-regulation of miR-9, miR-181c, miR-30c, miR-20b, miR-148b and Let-7i could be attributed at least in part to the presence of Aβ. [score:4]
In contrast to the above studies including ours, miR-9 was found to be up-regulated in human AD CA1 [34] and temporal cortex [35]. [score:4]
Our in vivo analysis of APP23 hippocampus showed down-regulation of miR-9, 181c, 30c, 20b, 148b and Let-7i, all of which were altered in human AD brain. [score:4]
miR-9 has also been reported to be down-regulated in an independent human profiling study of various brain regions including hippocampus [25]. [score:4]
Importantly, this human study showed that miR-9, 181c and Let-7i were down-regulated in AD brain. [score:4]
Axon guidance was among the most significant pathways to be affected by the predicted target genes and was the top prediction for miR-9, miR-30 and miR-20. [score:3]
It is encouraging to see that most of the pathways predicted to be affected by miR-9 target genes are related to brain function. [score:3]
Decreased expression of miR-9 may therefore impact adult brain function. [score:3]
Individual TaqMan assays (Applied Biosystems) were used to analyse the expression of the following mature mouse miRNAs: miR-181c, miR-9, miR-20b, miR-21, miR-30c, miR-148b, miR-361, miR-409-3p and Let-7i. [score:2]
In addition, an interesting overlap between human studies and ours was observed (miR-9, 181c, 30c, 148b, 20b and Let-7i) (Table 1) and therefore it was of great interest to validate and analyze these miRNAs in particular [13], [25]. [score:1]
Studies performed in zebrafish and mice revealed that miR-9 is essential in patterning, neurogenesis and differentiation and thus ideally placed to impact various aspects of brain function. [score:1]
miR-9, the most abundant human brain miRNA [53], is a recurring candidate from several AD profiling studies. [score:1]
Similarly, loss of miR-9 in zebrafish embryos decreases the relative numbers of differentiated neurons in the anterior hindbrain [54], [55], [56]. [score:1]
Interestingly, Aβ caused an extremely rapid neuronal response of distinct mature miRNA sequences with miR-9, 181c, 409-3p and 361 responding even after a one hour Aβ treatment. [score:1]
The decay rates for miR-9 are comparable in human brain tissue (T [1/2] = 48 min) and neuronal cells in culture (T [1/2] = 42 min), highlighting the validity of the in vitro mo del used by us. [score:1]
That the stability of mature miRNAs varies considerably was shown for the highly abundant, hepatocyte-specific microRNA miR-122 (T [1/2]>24 hrs) [48], while several brain-enriched miRNAs, such as miR-9, 125b, 146a, 132 and 183 exhibit short half-lives ranging from 1 to 3.5 hrs [35]. [score:1]
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[+] score: 56
To analyze the effect of miR-9, miR-96, miR-133b, and miR-146a on endogenous GDNF expression, we transiently overexpressed these miRNAs in U87 cells (a human glioblastoma cell line that expresses endogenous GDNF at detectable levels). [score:7]
We paid particular interest to miR-9 and miR-96, as previous data obtained from two genome-wide screens suggested that these miRNAs interact with Gdnf mRNA in the mouse brain; and overexpressing them in human cell line suppresses the expression of GDNF (summarized in [34]). [score:7]
Mutating some of the predicted miRNA seed sites (Fig 5C; see S1 for details) in the Gdnf 3’UTR either reduced or abolished the ability of miR-9, miR-96, miR-133a, and miR-146a to inhibit expression (Fig 5D), suggesting a direct interaction between these miRNAs and some of the predicted sites in the Gdnf 3’UTR. [score:6]
Based on this analysis, we identified the three shRNA constructs targeting miR-9, miR-96 and miR-146a with the highest potency for derepressing endogenous GDNF mRNA expression (Fig 5H). [score:5]
Finally, to gain insight into how endogenous miR-9, miR-96 and miR-146a impact endogenous GDNF mRNA levels in human cells we tested six different shRNA constructs targeted to each miRNA for their ability to derepress endogenous GDNF expression in HEK293 cells (S4M Fig). [score:5]
Our analysis of miRNA expression revealed that miR-9, miR-133a, miR-133b, miR-125a-5p, miR-125b-5p, miR-30a, miR-30b, and miR-146a are all expressed in the developing forebrain, adult dorsal striatum and in the developing kidney (S4 Table). [score:5]
We conclude that miR-9, miR-96, miR-133, and miR-146a interact directly with their binding sites in the Gdnf 3’UTR; moreover, miR-9, miR-96, and miR-146a regulate the expression of GDNF in vitro. [score:5]
Moreover, overexpressing miR-9, miR-96, miR-133b, and miR-146a represses the expression of endogenous GDNF mRNA and protein in a human cell line. [score:5]
Previously published genome-wide screens suggested that overexpressing miR-9 and miR-96 reduce the levels of GDNF mRNA in a human cell line and that these miRNAs interact with the Gdnf mRNA in the mouse brain [34]. [score:3]
We examined the miRNAs miR-133a, miR-133b, miR-125a-5p, miR-125b-5p, miR-30a, miR-30b, miR-96, miR-9, and miR-146a, which were selected based on their co -expression with Gdnf in several brain areas [17, 19, 32, 33]; see also www. [score:3]
miR-9, miR-96, miR-133 and miR-146a are novel regulators of GDNF. [score:2]
We identified binding sites for miR-9 and miR-96 in the 3’UTR of Gdnf; in addition, we identified binding sites for miR-133 and miR-146a. [score:1]
Finally, we found that shRNAs against miR-9, miR-96, and miR-146a derepress endogenous GDNF mRNA levels in human cell line. [score:1]
Note that miR-9/96/133m contains overlapping sites for miR-9, miR-96, and miR-133, all of which were mutated in this construct. [score:1]
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[+] score: 52
Highly expressed miRNAs included miR-124, miR-125a, miR-125b, miR-204 and miR-9. Over -expression of three miRNAs with significant predicted effects upon global mRNA levels resulted in a decrease in mRNA expression of five out of six individual predicted target genes assayed. [score:8]
The identity and expression pattern of those miRNAs which were detected by analysis of target gene expression, such as miR-124, miR-125 and miR-9, provides further evidence that miRNAs play a central role in neuronal differentiation during retinal development. [score:8]
Six genes targeted by three miRNAs with the highest expression and greatest predicted effects (miR-124; miR-125 and miR-9. ) were selected for validation: ACCN2; ETS1; KLF13; LIN28B; NFIB and SH2B3. [score:5]
Not surprisingly, these effects were related to the expression level of the miRNA; those with extremely significant effects, such as miR-125, miR-124 and miR-9 were amongst the most highly expressed in the P4 and adult murine retina. [score:5]
Notably, the transcription factor Hes1, which maintains retinal progenitor pools during development is a predicted target for miR-9 [50]. [score:4]
For example, miR-125, miR-124 and miR-9 have all been independently reported to be highly expressed in the retina [9- 11]. [score:3]
The following miRNAs had highly significant predicted effects on target mRNA levels and were selected for analysis by: miR-124, miR-125, miR-9, and miR-24. [score:3]
Decrease of miR-9 expression past P10 correlates with the completion of retinal cell differentiation. [score:3]
Following transfection of HEK293 cells with a pool of miR-124, miR-125 and miR-9 miRNA mimics the mRNA expression of 5 of these 6 genes was significantly reduced (Figure 6). [score:3]
This pattern is in agreement with Xu et al [11], who reported a very low level of miR-9 expression at E10 which gradually increased and peaked at P10, being lower in the adult retina. [score:3]
Expression of miR-9 was not detected in CE-RSCs, but in contrast to miR-124 it peaked in the P4 retina. [score:3]
At P4 many miRNAs had highly significant effects, with miR-124, miR-125 and miR-9 being particularly significant (Figure 1, Table 1 and Additional file 1: Table S1). [score:1]
Pools of miR-124, miR-125 and miR-9 miRNA mimics (miRNAs) or scrambled controls (Scrambled) were transfected into HEK293 cells. [score:1]
Together with miR-124 and miR-9, miR-125b is also induced during neural differentiation of embryonic stem cells [51]. [score:1]
miR-9 promotes progression of neurogenesis in the zebrafish brain [50]. [score:1]
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[+] score: 51
A miRNA array analysis revealed that among the miRNAs that are downregulated during osteoblastic differentiation, miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a, and miR-181a seemed most likely to target the osteogenesis-related transcription factors Dlx5 and Msx2, acting as potential inhibitors of osteogenesis by directly targeting these osteogenesis-related transcription factors. [score:11]
In our preliminary experiment, transfection of anti-miR-124a and anti-miR-181a did not induce osteoblastic differentiation in mouse iPS cells (data not shown), suggesting that suppression of miR-124a and miR181a, which directly target Dlx5 and Msx2, is not sufficient to induce osteoblastic differentiation of mouse iPS cells, but that suppression of at least one miRNA of miR-10a, miR-10b, miR-9-3p and miR-19b besides miR-124a and miR-181a is required for osteoblastic differentiation. [score:8]
We focused on the 6 miRNAs, miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a, and miR-181a that were significantly downregulated during BMP-4 -induced osteoblastic differentiation, and they seemed to target the transcription factors Dlx5 and Msx2 and to be associated with osteoblast differentiation (Table 3). [score:6]
A miRNA array analysis revealed that six miRNAs including miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a and miR-181a were significantly downregulated. [score:4]
The protocol shown in Fig. 5A was used to induce osteoblastic differentiation with 6 anti-miRNAs (anti-miR-124a, anti-miR-181a, anti-miR-10a, anti-miR-10b, anti-miR-9-3p, and anti-miR-19b) targeting Msx2 or Dlx5 in iPS cells. [score:3]
Six miRNAs including miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a, and miR-181a putatively targeted Dlx5 and Msx2 mRNA (Table 3). [score:3]
Considering the putative target genes in Table 3, miR-10a, miR-10b, miR-19b and miR-9-3p may constitute a control mechanism for Dlx5 and Msx2. [score:3]
0043800.g003 Figure 3 (A) Time course of miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a, and miR-181a expression in differentiated iPS cells. [score:3]
It is interesting that both miR-9-3p and miR-19b putatively target Id4, since Id4 has been reported to act as molecular switch promoting osteoblast differentiation [38]. [score:3]
In the present study, we demonstrate that six miRNAs including miR-10a, miR-10b, miR-19b, miR-9-3p, miR-124a and miR-181a miRNAs, especially miR-124a and miR-181a, are important regulatory factors in osteoblastic differentiation of mouse iPS cells. [score:2]
For functional studies examining the effects of the anti-miRNAs on cell differentiation, the mouse iPS cells were transfected on day 1 and day 8 after EB formation with anti-miR-124a, anti-miR-181a, anti-miR-10a, anti-miR-10b, anti-miR-19b, and anti-miR-9-3p for 72 h, followed by culture in GMEM without osteogenic factor. [score:1]
What are functions of these 6 miRNAs including miR-124a, miR-181a, miR-10a, miR-10b, miR-9-3p, and miR-19b in osteoblastic differentiation of mouse iPS cells? [score:1]
Although it has been reported that a number of miRNAs, miR-204/211 [13], miR-125b [14], miR-133 and miR-135 [15], miR-141 and miR-200a [16], and miR-29b [17], were involved in osteoblastic differentiation, a few papers have been reported with regard to the functions of miR-10a, miR-10b, miR-9-3p and miR-19b. [score:1]
0043800.g005 Figure 5(A) Schematic representation of the osteoblast differentiation protocol for iPS cells which were transfected with 6 anti-miRNAs including anti-miR-124a, anti-miR-181a, anti-miR-10a, anti-miR-10b, anti-miR-19b, and anti-miR-9-3p. [score:1]
Furthermore, miR-9-3p and miR-19b may affect JAK/STAT and MAPK pathways and MAPK and Wnt pathways, respectively. [score:1]
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[+] score: 40
Increased miR-9 would down-regulate REST and result in a net increase in prodynorphin expression, a result consistent with some morphine dosing patterns in a region specific manner (Przewłocka et al., 1996; Király et al., 2006). [score:6]
Figure 5Putative targeting miRNA's miR-27a and miR-9 increase Serpini1 expression. [score:5]
MiR-9 has also been implicated in regulation of the dynorphin κ-opioid receptor system via down-regulation of REST (Henriksson et al., 2014). [score:4]
MiR-9 is highly expressed in the nervous system and plays essential roles in neurogenesis, axon growth, dendritic development and regulation of the gene silencing transcription factor REST [repressor element 1 silencing transcription factor]/NRSF (neuron-restrictive silencer factor) that represses a large array of coding and noncoding neuron-specific genes important to synaptic plasticity (Giusti et al., 2014; Wang et al., 2016). [score:4]
Unexpectedly in a dual luciferase assay employing an mRNA reporter construct of the luciferase open reading frame fused to the Serpini1 3′UTR, luciferase protein expression was significantly increased by miR-27a [t [(4)] = 8.46, p = 0.011] (Figure 5) and another putative targeting miRNA, miR-9 [t [(4)] = 17.56, p < 0.001]; but not miR-206 (p > 0.05), a miRNA with no binding sites to Serpini1, and a nonsense sequence control. [score:4]
MicroRNA-9 controls dendritic development by targeting REST. [score:3]
MiR-9 was found to be overexpressed following COA and specifically by miR-27a (Figure 5). [score:3]
Renilla luciferase activity was normalized by firefly luciferase expression levels and is presented as percentage of activity achieved by the 3′-UTR of Serpini1 in the presence of mimics (miR27a, miR-9, miR-206, nonsense). [score:3]
MiR-27a and miR-9 target Serpini1 (mirSVR scores −1.9, −0.7, respectively) while miR-206 does not. [score:3]
MiR-27a and miR-9 increased Serpini1 expression, [***] p < 0.05. [score:3]
, Grand Island, NY) with 200 ng of psiCHECK2- Serpini1-3′ UTR plasmid and 5 pmol of Mus musculus (mmu)-miR-27a, mmu-miR-9, or nonsense mimics (Exiqon, Woburn, MA). [score:1]
Renilla luciferase values were normalized to control firefly luciferase levels (transcribed from the same vector but not affected by 3′ UTR tested) and averaged across 3–5 well repetition, resulting in 3–5 technical and 3 biological replicates for each condition (miR-9, 27-, 206, and nonsense control). [score:1]
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Effects of Dicer1-mutation on telencephalic miRNA levelsTo confirm the anticipated effects of Dicer1 deletion on mature miRNA production, we examined the expression of the two most abundant miRNAs in the E11.5 brain [28], [29]: miR-124, whose expression is restricted to the post-mitotic neuronal population [22], [30] and miR-9, which is expressed in both the progenitor and postmitotic cells [31]. [score:8]
To confirm the anticipated effects of Dicer1 deletion on mature miRNA production, we examined the expression of the two most abundant miRNAs in the E11.5 brain [28], [29]: miR-124, whose expression is restricted to the post-mitotic neuronal population [22], [30] and miR-9, which is expressed in both the progenitor and postmitotic cells [31]. [score:7]
Nonetheless, direct targeting of Sox9 mRNA by miRNAs other than miR-124, such as miR-9, remains a formal possibility as miRNAs have been shown to have the capacity to promote protein expression through non-canonical pathways, although very few examples have so far been reported [60], [61]. [score:6]
Mature miR-9 expression in the spinal cord, where Foxg1 is not normally expressed, was unaffected in the Dicer1 [-/-] embryos (Figure 1 D', E'). [score:5]
In control embryos at E11.5, miR-9 was strongly expressed throughout the thickness of the dorsal telencephalon (C) and the spinal cord (D). [score:3]
Expression of mature miR-9 in the spinal cord of the Dicer1 [-/-] embryos was not altered (D', E'). [score:3]
In the dorsal telencephalon of embryos with Foxg1 -driven Dicer1 deletion we found the level of mature miR-9 was depleted by E11.5 and was undetectable both in the cortex and in the diencephalon (Figure 1 C', F', G'). [score:1]
Mature miR-9 was depleted from the dorsal telencephalon by E11.5 (C', G'). [score:1]
Two abundant brain miRNAs, miR-124 and miR-9 were detected using LNA in situ hybridisation. [score:1]
High power images of the staining in the spinal cord (E), the diencephalon, which was devoid of mature miR-9 (F) and the dorsal telencephalon (G) in Dicer1 [-/-] embryos. [score:1]
The following RNA probes were used for in situ hybridisations: Dlx2 (generous gift from John Rubenstein), Emx2 (generous gift from Antonio Simeone), Erbb2 (generous gift from Carmen Birchmeier), Foxg1 [37], generous gift from Thomas Theil), mmu-miR-124-1 (Exiqon, DK), mmu-miR-9 (Exiqon, DK), Ngn2 (generous gift from Thomas Theil). [score:1]
In the forebrain of control embryos, mature miR-9 is present throughout the thickness of the dorsal telencephalic wall (Figure 1 C, G) and in the spinal cord at E11.5 (Figure 1 D - E) but was undetectable in the diencephalon (Figure 1 C, F). [score:1]
0023013.g001 Figure 1Loss of mature miR-124 and miR-9 in the telencephalon of Dicer1 [-/-] embryos. [score:1]
Loss of mature miR-124 and miR-9 in the telencephalon of Dicer1 [-/-] embryos. [score:1]
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19
[+] score: 39
Inhibition of FGF signaling through SU5402 -treated primitive streak regions of chick embryos identified up-regulation of let-7b, miR-9, miR-19b, miR-107, miR-130b, miR-148a, miR-203, and miR-218 and down-regulation of miR-29a and miR-489 (Bobbs et al. 2012). [score:9]
In contrast, expression of miR-9 and miR-203 was induced by FGF2 in lens, although they were induced via inhibition of FGF receptors in the embryonic chick mo del (Bobbs et al. 2012). [score:5]
Figure 11Analysis of miR-9, -143, -301a, -381, and -455 expression pattern during embryonic and postnatal lens development. [score:4]
To determine whether the aforementioned miRNAs identified in rat lens explant system are also expressed during mammalian lens development in vivo, we conducted ISH analysis of miR-9, miR-143, miR-155, miR-301a, miR-381, and miR-455 in E14.5 and newborn (P0) lenses. [score:4]
The current data suggest that multiple miRNAs, including miR-9, miR-137, miR-155, miR-301a, miR455, and miR-543 (Figure 7A and Figure 8A), regulate c-Maf expression through its 3′-UTR. [score:4]
We conclude that miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543 represent an FGF2 -dependent system of multiple miRNAs that target specific genes operating in pathways and processes related to the lens differentiation (via c-Maf, Med1/PBP, N-myc, and Nfat5), miRNA-regulated RNA processing (via Cpsf6 and Tnrc6b) and nuclear/chromatin -based processes (via Med1/PBP, As1l, and Kdm5b/Jarid1b/Plu1). [score:4]
At E14.5, the miR-9 (A), -143 (C), -301a (E), -381 (G), and -455 (I) expression domain included the monolayer of lens epithelial cells, the proliferating lens cells, the migrating lens cells, and the differentiating lens cells. [score:3]
We found that seven miRNAs, including miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543, target at least two “early” genes examined (i. e., c-Maf, N-Myc, and Nfib). [score:3]
At postnatal day P0, the distribution of both miR-9 (B) and miR-143 (D) is largely maintained in all the lens cells previously described for the E14.5 lens, whereas miR-301a (F) is not detected. [score:1]
Seven miRNAs, including miR-9, miR-137, miR-200c, miR-381, miR-455, miR-495, and miR-543, and connections to specific functional groups of genes are shown. [score:1]
The most connected miRNA identified here through the 12 top-ranking transcripts, including miR-495, miR-200c, miR-543, miR-381, and miR-9 (Figure 6A), retained their high-connectivity positions as identified by independent analysis shown earlier in Figure 6A. [score:1]
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[+] score: 37
Mir-9 and mir-124, the two most abundant miRNAs in the CNS, showed different responses to VPA treatment: while mir-124 was downregulated, no effect on mir-9 expression could be observed after VPA exposure. [score:6]
As expected, the substance did not affect the expression of pri -mir-9. A. Expression of mature miRNAs. [score:5]
As expected, the substance did not affect the expression of pri -mir-9. In order to verify whole genome microarray data by real-time RT-PCR, we selected genes known to be involved in the development and neural tube closure (Hox genes, Twist1, Hamga2, Pax6, Otx1, Otx2, Zic4 and Zic5, Fzd4, Dkk2, Vcl), as well as muscle-specific Actc1. [score:4]
Myogenesis regulating mir-206 is highly expressed in skeletal muscles in both species [62], [63] as is mir-124, mir-9, mir-128 and mir-137 in mouse and human brain where they are responsible for fine-tuning of neurogenesis [62] [64]. [score:4]
F. Expression of neuronal specific markers mir-9, mir-124 and β-III-tubulin and neuro-progenitor specific marker nestin at different time points of neural differentiation. [score:3]
These results suggest that VPA affects neural differentiation processes and pathways, which are specific for mir-124 but not mir-9. Exposure of differentiating mESCs to VPA also reduced expression of mir-128, which is an enhancer of neural differentiation [88]. [score:3]
mir-9 was strongly induced from day 9 of differentiation onwards, while mir-124 and mir-128 were induced later on reaching their maximum expression levels both on day 16 ([47] and Fig. S1F). [score:3]
mir-9 expression was not changed significantly upon 16 days of VPA treatment. [score:3]
We did not observe any changes in the expression of neuro-specific mir-9 in our microarray data, so this miRNA was included in RT-PCR analysis as a negative control. [score:3]
Most regulated miRNAs shown in our study are highly conserved between mice and humans (e. g. mir-206, mir-214, mir-10a, mir-124, mir-137, mir-128, mir-9) [61], [62]. [score:2]
A slight induction of mir-9 was observed at the highest concentrations of TSA (Fig. 9). [score:1]
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[+] score: 35
Taken together, our findings suggest that potential UCP1 -targeting miR-9 and miR-338-3p may be involved in the process of the browning of epididymal adipose tissue through posttranscriptional suppression of UCP1 gene expression. [score:7]
Compared with control group, as shown in Figure 3(b), the expression of miR-9 and miR-338-3p was significantly restrained in epididymal adipose tissue with CL316243 treatment (P < 0.05), and miR-let7g (not UCP1 -targeting miRNAs, as negative control) expression had no statistical differences (P > 0.05). [score:6]
A panel of 2 miRNAs, namely, miR-9 and miR-338-3p, was selected for its putative ability to target the 3′-UTRs of UCP1 mRNA (Figure 3(a)). [score:3]
We proposed that β3-adrenergic stimulations might restrain expression of miR-9 and miR-338-3p in the epididymal adipose tissue in mice. [score:3]
Clearly, we need to identify whether miR-9 and miR-338-3p are the potential candidates that target UCP1. [score:3]
These results seemed to strictly correlate with an increase in UCP1 mRNA, confirming the hypothesis that CL316243 could reduce miR-9 and miR-338-3p expression leading to reducing the degradation of UCP1 messenger RNA. [score:3]
Expressions of miR-9 and miR-338-3p in the Epididymal Adipose Tissue of Mice with CL316243 Treatment. [score:3]
Here we showed that miR-9 and miR-338-3p which possibly targeted UCP1 were dramatically decreased with CL316243 treatment. [score:3]
Primers for miR-9, miR-338-3P, miR-let7g, and U6 were listed in Table 1. The relative expressions among the different genes and miRNAs were determined using the 2 [−ΔΔCT] method. [score:2]
Primers for miR-9, miR-338-3P, miR-let7g, and U6 were listed in Table 1. The relative expressions among the different genes and miRNAs were determined using the 2 [−ΔΔCT] method. [score:2]
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[+] score: 34
miR-33b overexpression results in down-regulation of miR-9. miR-33b reduces cell migration. [score:6]
Lovastatin treatment led to miR-33b upregulation and lowered expression of miR-9, c-Myc and cyclin E in tumours of Daoy cells, but not in tumours of D283 cells (Fig 5B–D; Supporting Information Fig S11B). [score:6]
We found that miR-33b reintroduction down-regulated the expression of miR-9 (Fig 2D) and resulted in a reduction in cell migration (Fig 2E). [score:6]
B. miR-33b expression was elevated and miR-9 was down-regulated in tumours with Daoy cells upon lovastatin treatment. [score:6]
In addition, miR-33b overexpression led to a larger percentage of Daoy cells arrested at the G1 phase (Supporting Information Fig S7C), decreased cell proliferation (Supporting Information Fig S7D), and lowered miR-9 expression (Supporting Information Fig S7E) along with reduced cell migration (Supporting Information Fig S7F). [score:5]
miR-9 is a transactivational target of c-Myc and regulates cell migration and tumour metastasis (Ma et al, 2010). [score:4]
Over a dozen miRNAs such as the miR-17–92 cluster (He et al, 2005; O'Donnell et al, 2005) and miR-9 (Ma et al, 2010) have been found to be induced by c-Myc to manifest its function in cell cycle, survival, metabolism, apoptosis and metastasis (Bui & Men dell, 2010). [score:1]
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[+] score: 34
In cerebellar development, VEGF is co-expressed with late-expressed miR-125, whereas E-cadherin and P21 are either not significantly changed or are co-expressed with late miR-9 and miR-22, respectively, in another series (personal communication with J. M. Lee). [score:8]
Interestingly, both miR-124 (a highly brain-specific miRNA) and miR-9 (a highly functional miRNA in brain development) are expressed late in development and are significant when their non-coherent targets are compared with the non-target control gene set. [score:8]
Unlike the shared program described between developing cerebellum and MB, only three terms such as activator, DNA binding, and DNA metabolism, were shared between small cell lung cancer upregulated genes and coherent targets in developing lung, involving miR-30, miR-200a, and miR-9, respectively. [score:6]
A total of 11 miRNAs, let-7, miR-9, miR-206, miR-138, miR-133, miR-152, miR-137, miR-128, miR-143, miR-27b and miR-218 were co-expressed by 18 synaptic transmission target genes (Table S6). [score:5]
For synaptic transmission, miR-128, miR-27b, miR-133, miR-206, miR-152 and miR-9 are shared between development and tumor using picTar prediction; miR-128, miR-140, miR-27b, miR-22, miR-133, miR-223 and miR-152 are shared using PITA prediction. [score:2]
Again, the GO processes were composed of two sub-trees (Figure 3B), as in development, for shared miRNAs, such as miR-9, miR-206, miR-138, miR-133, miR-152, and miR-128. [score:2]
In addition, the fact that NRSF is not significantly differentiated in brain tumors suggests that NRSF might not form a Type I circuit with miR-9 in brain tumors. [score:1]
As miR-9 is reported to have a matched binding motif with neuronal repressor NRSF/REST [39], NRSF might be a promoter that acts in the Type I circuit. [score:1]
For brain tissues, miR-9 and miR-128b are Type I, although miR-128b is not found in the motor neuron data [38]. [score:1]
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[+] score: 32
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-20a, hsa-mir-21, hsa-mir-29a, hsa-mir-33a, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-124-3, mmu-mir-126a, mmu-mir-9-2, mmu-mir-132, mmu-mir-133a-1, mmu-mir-134, mmu-mir-138-2, mmu-mir-145a, mmu-mir-152, mmu-mir-10b, mmu-mir-181a-2, hsa-mir-192, mmu-mir-204, mmu-mir-206, hsa-mir-148a, mmu-mir-143, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-204, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-143, hsa-mir-145, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-134, hsa-mir-138-1, hsa-mir-206, mmu-mir-148a, mmu-mir-192, 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-21a, mmu-mir-29a, mmu-mir-29c, mmu-mir-34a, mmu-mir-330, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-107, mmu-mir-17, mmu-mir-212, mmu-mir-181a-1, mmu-mir-33, mmu-mir-211, mmu-mir-29b-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-106b, hsa-mir-29c, hsa-mir-34b, hsa-mir-34c, hsa-mir-330, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, hsa-mir-181d, hsa-mir-505, hsa-mir-590, hsa-mir-33b, hsa-mir-454, mmu-mir-505, mmu-mir-181d, mmu-mir-590, mmu-mir-1b, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, mmu-mir-126b, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1
Inhibition of miR-9 leads to derepression of Dicer (Leucci et al., 2012); it suppresses matrix metalloproteinase (MMP)-14 expression via binding to a site in the 3′-UTR, thus inhibiting the invasion, metastasis, and angiogenesis of neuroblastoma (Zhang et al., 2012a). [score:9]
The bifunctional microRNA miR-9/MIR-9* regulates REST and co-REST and is downregulated in Huntington’s disease. [score:7]
Downregulation of the miR-9 gene changes the stoichiometry of axonal neurofilaments (upregulates a gene coding for a heavy neurofilament subunit) in a mouse mo del of human spinal muscular atrophy characterized by anterior horn sclerosis, aberrant end plate architecture, and myofiber atrophy with signs of denervation (Haramati et al., 2010), while it is overexpressed in several cancer forms, including brain tumors, hepatocellular carcinomas (HCC), breast cancer, and Hodgkin lymphoma. [score:7]
microRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells. [score:5]
Inhibition of miR-9 de-represses HuR and DICER and impairs Hodgkin lymphoma tumor outgrowth in vivo. [score:3]
MicroRNA-9 directs late-organizer activity of the midbrain-hindbrain boundary. [score:1]
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[+] score: 32
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-17, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-32, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-106a, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-30b, mmu-mir-126a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-137, mmu-mir-140, mmu-mir-150, mmu-mir-155, mmu-mir-24-1, mmu-mir-193a, mmu-mir-194-1, mmu-mir-204, mmu-mir-205, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-143, mmu-mir-30e, hsa-mir-34a, hsa-mir-204, hsa-mir-205, hsa-mir-222, mmu-let-7d, mmu-mir-106a, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-30b, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-137, hsa-mir-140, hsa-mir-143, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-150, hsa-mir-193a, hsa-mir-194-1, mmu-mir-19b-2, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-mir-200a, 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-23a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-92a-2, mmu-mir-34a, rno-mir-322-1, mmu-mir-322, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-140, rno-mir-350-1, mmu-mir-350, hsa-mir-200c, hsa-mir-155, mmu-mir-17, mmu-mir-25, mmu-mir-32, mmu-mir-200c, mmu-mir-33, mmu-mir-222, mmu-mir-135a-2, mmu-mir-19b-1, mmu-mir-92a-1, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-30e, hsa-mir-375, mmu-mir-375, mmu-mir-133b, hsa-mir-133b, 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-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-17-1, rno-mir-19b-1, rno-mir-19b-2, rno-mir-23a, rno-mir-24-1, rno-mir-24-2, rno-mir-25, rno-mir-27b, rno-mir-29a, 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-32, rno-mir-33, rno-mir-34a, rno-mir-92a-1, rno-mir-92a-2, rno-mir-106b, rno-mir-126a, rno-mir-135a, rno-mir-137, rno-mir-143, rno-mir-150, rno-mir-193a, rno-mir-194-1, rno-mir-194-2, rno-mir-200c, rno-mir-200a, rno-mir-204, rno-mir-205, rno-mir-222, hsa-mir-196b, mmu-mir-196b, rno-mir-196b-1, mmu-mir-410, hsa-mir-329-1, hsa-mir-329-2, mmu-mir-470, hsa-mir-410, hsa-mir-486-1, hsa-mir-499a, rno-mir-133b, mmu-mir-486a, hsa-mir-33b, rno-mir-499, mmu-mir-499, mmu-mir-467d, hsa-mir-891a, hsa-mir-892a, hsa-mir-890, hsa-mir-891b, hsa-mir-888, hsa-mir-892b, rno-mir-17-2, rno-mir-375, rno-mir-410, mmu-mir-486b, rno-mir-31b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-499b, mmu-let-7j, mmu-mir-30f, mmu-let-7k, hsa-mir-486-2, mmu-mir-126b, rno-mir-155, rno-let-7g, rno-mir-15a, rno-mir-196b-2, rno-mir-322-2, rno-mir-350-2, rno-mir-486, mmu-mir-9b-2, mmu-mir-9b-1
These candidate miRNAs included representatives that exhibited regulated patterns of expression from each of the two primary classes detected, namely: those with highest expression in the caput (let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p), or highest expression in the cauda (miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:8]
0135605.g008 Fig 8In order to verify the next generation sequence data, nine differentially expressed miRNAs were selected for targeted validation using qRT-PCR, including representatives with highest expression in the proximal (caput: let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p) and distal (cauda: miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:7]
In order to verify the next generation sequence data, nine differentially expressed miRNAs were selected for targeted validation using qRT-PCR, including representatives with highest expression in the proximal (caput: let-7c-5p, let-7b-5p, miR-375-3p, miR-9-5p, miR-467d-3p, and miR-200c-3p) and distal (cauda: miR-410-3p, miR-486-5p, and miR470c-5p) epididymis. [score:7]
It also highlighted the caput-specific expression of miR-9-5p, and confirmed a significant up-regulation of miR-486-5p and miR470c-5p between the caput and corpus epididymis. [score:6]
Similarly, within the differentially expressed pool of miRNAs, 10 were identified that are intimately involved in regulating intracellular trafficking pathways, including: miR-7b-5p, miR-9-5p, miR-31-5p, miR-92a-3p, miR-106-5p, miR-126-3p, miR-150-5p, miR-204-5p, miR-222-3p, and miR-322-5p (S2 Fig). [score:4]
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[+] score: 30
Two miRNAs (miR-9-5p and miR-183-5p) were regulated by O [3], and these were shown to target the NF-kB protein and mRNA experimentally (Western blot and qRT-PCR) [46] and by in silico analysis (TargetScan). [score:6]
miR-9-5p expression levels were downregulated. [score:6]
miR-9-5p expression levels were downregulated significantly compared to control, and this may increase NF-kB mRNA levels that in turn may induce anti-proliferative effects [72]. [score:5]
This mRNA is targeted by miR-9-5p [47], miR-21-5p, miR-16-5p (TargetScan), miR-183-5p [47], miR-486b-5p [82], and miR-153-3p [47]. [score:5]
Two miRNAs (miR-9-5p and miR-183-5p) were significantly changed by O [3], and these were shown to target the NF-kB mRNA experimentally [46] and by in silico analysis (TargetScan), respectively. [score:5]
FOXO1 is targeted by a multitude of miRNAs that are changed in our study miR-9-5p, miR-21-5p, miR-16-5p, miR-183-5p [47], miR-486b-5p, and miR-153-3p. [score:3]
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27
[+] score: 27
LPS down-regulates AChR expression resulting in acetylcholine increase, down-regulates α7 nAChR expression and changes the levels of miR-132/212, miR-9, miR-99 and let-7g. [score:11]
The brain-abundant miRNA-9, which was down-regulated by LPS exposure, inhibits the expression of a proapoptotic Bcl-2L11 found in the outer mitochondrial membrane (Li et al., 2014); its potential pro-apoptotic effect was largely avoided by the antibody. [score:8]
MiR-9 was up-regulated by nicotine and much less affected by the LPS; however, again, the antibody effect was opposite to that of LPS. [score:3]
MicroRNA-9 regulates neural apoptosis in methylmalonic acidemia via targeting BCL2L11. [score:3]
The effects of nicotine and LPS were of similar direction for six miRs (miR-26, let-7f, let-7c, miR-30, miR-21a and miR-434) and showed an opposite impact for other four miRs (miR-9, let-7j, miR-218 and miR-125). [score:2]
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Of these differentially expressed miRNAs, miR-27b (downregulated in OA) directly targets MMP-13 expression (Stone et al., 2011); miR-22 (upregulated in OA) directly regulates PPARA and BMP-7 expression in cartilage; miR-9 inhibits MMP13 secretion in isolated human chondrocytes; and miR-146a is highly expressed in early OA cartilage and has been shown to control knee joint homeostasis and OA -associated algesia by balancing inflammatory responses in the cartilage and synovium. [score:22]
For example, miR-9 contributes to regulating MMP-13, miR-98 and miR-146, which are important for controlling the expression of tumor necrosis factor α (Jones et al., 2009). [score:4]
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Next to miR-204, the next most highly expressed MG miRNAs (with less than 20% expression in neurons) were miR-125b, and miR-9. These two miRNAs are also highly expressed in P7 FAC-sorted astrocytes of the forebrain, along with several others of the most highly expressed mGliomiRs (miR-99a, miR-204, miR-135a) and shared miRs (miR-720, let-7b, miR-29a, and miR-30d) 40. [score:9]
Three of the top four miRNAs expressed in adult MG, miR-204, miR-125-5p and miR-181a, showed large increases in their expression between the P11 and adult, while miR-9, did not increase. [score:5]
miR-204, miR-125b-5p, and miR-9 are the top 3 mGliomiRs, and showed 18, 9 and 7 fold higher levels of expression in MG than in neurons. [score:3]
For example, miR-204, miR-9, and miR-181a, the most highly expressed miRNAs in MG, showed the greatest decline in vitro, together with some members of the let-7 family. [score:3]
Moreover, miR-9 is also required for Bergmann glia development in the cerebellum 49. [score:2]
A role for miR-125b and miR-9 has been described for retinal development, particularly in the transition from early (non-gliogenic) to late (gliogenic) progenitors 41, as well as its role during neurogenesis 42 43. [score:2]
Thus, miR-125 and miR-9 appear to have general roles in neural progenitors to convey competency to generate glia. [score:1]
The miRNAs that decline the most over the culture period include miR-204, miR-9 and most members of the let-7 family. [score:1]
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A good example of a microRNA with expression in both embryonic and adult neurogenesis is the brain-enriched microRNA miR-9. miR-9 suppresses the expression of key transcriptional regulators of NSCs during development, including Hes1, Tlx and REST (Packer et al., 2008; Zhao et al., 2009; Bonev et al., 2012; Tan et al., 2012; Coolen et al., 2013). [score:9]
The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. [score:7]
MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain. [score:3]
Although miR-9 expression has been detected in the adult neurogenic niches in mice, functional studies have not been performed yet (Deo et al., 2006; Kapsimali et al., 2007). [score:3]
A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. [score:2]
miR-9: a versatile regulator of neurogenesis. [score:2]
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31
[+] score: 26
Upregulated genes included miR-9, which was previously shown to inhibit cancer metastasis by suppressing e-cadherin [30], and miR-221 [31], which contributes to liver tumorigenesis. [score:8]
Downregulated genes that clustered with miR-101 and upregulated genes that clustered with miR-9 were magnified within the figure. [score:7]
Most notably, miR-9, which was upregulated in nicotine -treated cells, has been shown to promote metastasis in breast cancer by repressing E-cadherin [30]. [score:4]
The roles of miR-9 and other differentially expressed miRNAs remain to be fully established in the context of nicotine -induced EMT, and should be addressed by future experiments. [score:3]
B) qPCR validation of miR-9 and miR-101 expression. [score:3]
miR-9 has also been shown to control the migration and proliferation of progenitor cells derived from hESCs [36]. [score:1]
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[+] score: 25
Similarly, no difference between NF-kB levels was observed between the M12 or M12+miR-9 inhibited cells (Fig 4f and 4g). [score:3]
Four of the five M12 injected mice developed tumours, but only two of the five M12+miR-9 inhibited mice developed tumours, which grew at a slower rate and size. [score:3]
Inhibition of (M12+miR-9-Inh) resulted in rescue of e-cadherin mRNA. [score:3]
miR-9. E-Cadherin message and protein levels are suppressed by miR-9. miR-9’s mode of action on tumour progression through e-cadherin and SOCS5. [score:3]
SOCS5 protein levels are suppressed by miR-9. Conclusions. [score:3]
Targetscan analysis of miR-9 seed region binding site to SOCS5 3’-UTR (NM_014011.4) reveals high level of sequence conservation among species. [score:3]
Intraprostatic injection resulted in 7 metastatic sites for M12 -injected mice, while neither of the M12+miR-9 inhibited mice had any observed metastatic sites by 76 days after injection (Fig 3b). [score:3]
miR-9 was not a surprising find as dysregulated in prostate cancer. [score:2]
miR-9 was chosen for further analysis, given its known role in other neoplasias and well-characterized proven targets [10, 28– 36]. [score:1]
Evaluation of SOCS5 mRNA levels showed no significant differences between P69, M12, M12 cells stably transformed with a scrambled RNA sequence (M12+Scr) or stably transformed with the inhibitor (M12+miR-9-Inh) (Fig 5a). [score:1]
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[+] score: 24
The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. [score:7]
MicroRNA Function Target/s Reference microRNAs involved in neural development let-7 Promotes neuronal differentiation HMGA, LIN28, TLX Nishino et al. (2008), Rybak et al. (2008), Zhao et al. (2010) Neural tube closure MLIN41 Maller Schulman et al. (2008) miR-7a Inhibits differentiation of forebrain dopaminergic neurons PAX6 de Chevigny et al. (2012) miR-9 Promotes neuronal differentiation FOXG1, TLX, STAT3, REST, FGF8, FGFR1, FOXP2 Krichevsky et al. (2006), Leucht et al. (2008), Packer et al. (2008), Shibata et al. (2008), 2011, Zhao et al. (2009), Yoo et al. (2011), Clovis et al. (2012) Promotes proliferation of early human embryonic stem cell-derived neural progenitor cells STMN1 Delaloy et al. (2010) miR-9* Promotes neuronal differentiation BAF53a Yoo et al. (2009), 2011 ? [score:6]
MicroRNA-9 modulates Cajal–Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. [score:4]
MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors. [score:3]
A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. [score:2]
Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons. [score:1]
MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. [score:1]
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[+] score: 23
Selection of the differentially expressed miRNAs under the relatively strict conditions (≥500 sequence reads in at least one of the libraries selected for comparison, ≥5-fold difference in expression, and a p value of ≤ 0.01) identified nine upregulated miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p, miR-340-5p, miR-381-3p, miR-411-5p, miR-9-5p, and miR-219-2-3p) at 3 d, but none at 7 d or 14 d, suggesting that these upregulated miRNAs impact biological functions, particularly during the early stages after nerve allotransplantation with FK506 immunosuppression. [score:13]
Among these nine upregulated circulating miRNAs, miR-9-5p had the highest fold-change of ≥50-fold, followed by miR-340-5p with 38.8-fold. [score:4]
Among the nine upregulated miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p, miR-340-5p, miR-381-3p, miR-411-5p, miR-9-5p, and miR-219-2-3p), miR-9-5p had the highest fold-change (≥50-fold at 3 d), followed by miR-340-5p with 38.8-fold. [score:4]
Correlation of miR-9-3p with the genes involved in immune/inflammatory responses (e. g., IFNG and IL17F), apoptosis (e. g., PDCD4 and PTEN), and cell proliferation (e. g., NKX3-1 and GADD45A) has been reported in stimulated human peripheral blood lymphocytes [20]. [score:1]
Nine candidate miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p, miR-340-5p, miR-381-3p, miR-411-5p, and miR-9-5p) were identified. [score:1]
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[+] score: 20
Expression of miR-9 increases on a timescale equivalent to the down-regulation effects on KCNMA1 mRNA. [score:6]
miR-9 is predicted to target ALCOREX-containing KCNMA1 mRNAs based on the presence of and complementarity with an alternative 3'UTR (called 3'UTR-2.1) that is associated with ALCOREX-containing mRNAs (Pietrzykowski et al., 2008). [score:3]
These data identify miR-9 as a key regulator of BK channel ethanol tolerance although the in vivo consequences of this regulation remains to be tested, particularly in combination with beta subunit effects on sensitivity and tolerance. [score:3]
Very acutely, KCNMA1 expression in rats is decreased by miR-9 in response to ethanol treatment, but induction of KCNMA1 has been observed in mice in separate studies in specific brain regions 4 h after an injection of ethanol. [score:3]
The well-established roles for the microRNA miR-9 and the BK β subunits in altering BK function, and, specifically, in modifying the ethanol responsiveness of BK, make them excellent targets for study. [score:3]
Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. [score:2]
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36
[+] score: 20
Finally, miR-375, miR-138 and miR-9 were selected for further analysis due to their down-regulation in clinical samples and their ability to induced phenotypic changes in vitro. [score:4]
To validate the identified phenotypes, the miRNAs that were down-regulated in clinical samples and Top-40 ranked in the phenotype screen (miR-150, miR-375, miR23b, miR-138, miR-139-5p and miR-9) were subjected to detailed functional analysis using HCT116, HT29, LS174T TR4, DLD1 TR7 and SW480 colon cancer cell lines. [score:4]
The ectopic expression of miR-375, miR-9 and miR-138 significantly reduced the viability of more than one cell line (MTT reduction >20% and p≤0.05) (Figure 2A (HCT116) and Figure S2), possible due to a general anti-proliferative or pro-apoptotic role of these miRNAs. [score:3]
miR-9 and miR-138 were expressed primarily by stromal cells from both normal colon mucosa and adenocarcinomas (Figure S4). [score:3]
Figure S4 The expression of miR-9 and miR-138 in laser capture microdissected colorectal cancer tissue. [score:3]
In conclusion, the validation analysis confirmed the anti-proliferative role of miR-9 and miR-138, and the apoptosis inducing capacity of miR-375 as identified in the high-throughput analysis. [score:1]
Detection of miR-375, miR-138 and miR-9 in laser microdissected colorectal tissue. [score:1]
To elucidate the cellular origin of miR-375, miR-138 and miR-9, we measured their expression in laser captured microdissected colorectal adenocarcinomas and adjacent normal colon mucosa (Figure 2E and Figure S4). [score:1]
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[+] score: 20
Other miRNAs from this paper: hsa-let-7c, hsa-let-7d, hsa-mir-16-1, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-28, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-99a, hsa-mir-101-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-27b, mmu-mir-30a, mmu-mir-99a, mmu-mir-101a, mmu-mir-125b-2, mmu-mir-126a, mmu-mir-128-1, mmu-mir-9-2, mmu-mir-142a, mmu-mir-144, mmu-mir-145a, mmu-mir-151, mmu-mir-152, mmu-mir-185, mmu-mir-186, mmu-mir-24-1, mmu-mir-203, mmu-mir-205, hsa-mir-148a, hsa-mir-34a, hsa-mir-203a, hsa-mir-205, hsa-mir-210, hsa-mir-221, mmu-mir-301a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-27b, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-142, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-126, hsa-mir-185, hsa-mir-186, mmu-mir-148a, mmu-mir-200a, mmu-let-7c-1, mmu-let-7c-2, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-21a, mmu-mir-24-2, mmu-mir-29a, mmu-mir-31, mmu-mir-34a, mmu-mir-148b, mmu-mir-339, mmu-mir-101b, mmu-mir-28a, mmu-mir-210, mmu-mir-221, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-125b-1, mmu-mir-128-2, hsa-mir-128-2, hsa-mir-200a, hsa-mir-101-2, hsa-mir-301a, hsa-mir-151a, hsa-mir-148b, hsa-mir-339, hsa-mir-335, mmu-mir-335, hsa-mir-449a, mmu-mir-449a, hsa-mir-450a-1, mmu-mir-450a-1, hsa-mir-486-1, hsa-mir-146b, hsa-mir-450a-2, hsa-mir-503, mmu-mir-486a, mmu-mir-542, mmu-mir-450a-2, mmu-mir-503, hsa-mir-542, hsa-mir-151b, mmu-mir-301b, mmu-mir-146b, mmu-mir-708, hsa-mir-708, hsa-mir-301b, hsa-mir-1246, hsa-mir-1277, hsa-mir-1307, hsa-mir-2115, mmu-mir-486b, mmu-mir-28c, mmu-mir-101c, mmu-mir-28b, hsa-mir-203b, hsa-mir-5680, hsa-mir-5681a, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, hsa-mir-486-2, mmu-mir-126b, mmu-mir-142b, mmu-mir-9b-2, mmu-mir-9b-1
Furthermore, some of the differentially expressed miRNAs have been reported to play a role in the metastasis of other types of cancer, for example, the up-regulated miRNAs, let-7i, miR-9, miR-30a, miR-125b, miR-142-5p, miR-151-3p, miR-450a and the down-regulated miRNAs, miR-24, mir-145, miR-146b-5p, miR-185, miR-186, miR-203 and miR-335. [score:9]
Of the up-regulated miRNAs in the metastatic line, miR-9 has been reported to target E-cadherin [64] and CDH1, the E-cadherin-encoding messenger RNA [65]; overexpression of miR-9 in non-metastatic breast tumor cells enables such cells to form pulmonary micrometastases in mice [65]. [score:8]
One-base-shift forms of miR-9*, miR-148b* and miR-1246 showed higher expression than the reference forms in both metastatic and non-metastatic lines. [score:3]
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[+] score: 19
A circRNA from the Zfyve9 gene (mm9_circ_014815) that was age -upregulated in hippocampus harbored several different microRNA target sites: 3 target sites for miR-9, a microRNA with roles in neural development and neural pathologies 32, 1 target site for miR-124, a highly abundant brain miRNA that is implicated in central nervous system disorders 33, and 1 miR-7 target site (Supplementary Table S13). [score:13]
In addition, a cortex age -upregulated circRNA from the Acin1 gene (mmu_circ_0005278) harbored 4 target sites for miR-9, (Supplementary Tables S10 and S13, Supplementary Fig. S4). [score:6]
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[+] score: 19
Figure 2B shows the results of miRNA abundance in bar-graph format of these 3 miRNAs in aluminum-fed over magnesium-sulfate fed controls; both miRNA-9 and miRNA125b showed modest up-regulation to ~1.8 and 2.1-fold over control, respectively, in aluminum sulfate fed animals; the most significantly up-regulated miRNA in these studies was the inflammation and neurodegeneration -associated miRNA-146a to about ~9.1-fold over controls in blood serum after 5 months. [score:7]
miRNA increases appear to be the consequence, in part, of an inducible miRNA-9, miRNA-125b and miRNA-146a being up-regulated under conditions of stress as has been observed in both human neuronal-glial (HNG) primary cells and in human brain obtained from short post-mortem interval AD tissue samples [18, 21, 22]. [score:4]
The purpose of the current research work was to quantify the concentrations and clarify the contributions of CRP, IL-6, TNFα and the levels of the pro-inflammatory microRNAs, including miRNA-9, miRNA-125b and miRNA-146a, in the blood serum of wild-type C57BL/6J mice that were fed aluminum-sulfate in their diet over a time course of 0, 1, 3 and 5 months. [score:1]
After 5 months of aluminum-sulfate ingestion by C57BL/6J mice, all 6 biomarkers (CRP, IL-6, TNFα, miRNA-9, miRNA-125b and miRNA-146A) were found to exhibit increases in the blood serum, indicating a significant stimulation of SI biomarkers in aluminum-sulfate fed animals. [score:1]
This study is the first to show that the circulating cytokines IL-6 and TNFα, CRP and the pro-inflammatory microRNAs miRNA-9, miRNA-125b and miRNA-146 are elevated in mouse blood serum after ingestion of physiologically realistic amounts of aluminum (as sulfate) in the diet. [score:1]
Figure 2A shows the levels of 3 serum and brain-abundant microRNAs (miRNA-9, miRNA-125b and miRNA-146a) and controls (miRNA-183 and 5S RNA); C1 and C2=blood serum from 2 control C57BL/6J mice receiving magnesium sulfate in their diet; A1 and A2=blood serum from 2 C57BL/6J mice receiving aluminum sulfate in their diet. [score:1]
Systemic Inflammation, CRP, IL-6, TNFα, miRNA-9, miRNA-125b and miRNA-146a. [score:1]
sncRNA abundance analysis including microRNA (miRNA) abundance analysis for miRNA-9, miRNA-125b, miRNA-146a, miRNA-183 and 5S RNA were quantified using microfluidic sncRNA and miRNA arrays as previously described in detail (LC Sciences, Houston TX, USA) [11, 18, 21]. [score:1]
Increases in small non-coding RNA (sncRNA) microRNAs miRNA-9, miRNA-125b and miRNA-146a. [score:1]
While miRNA-9 and miRNA-125b displayed modest increases in abundance in the blood serum of C57BL/6J mice after aluminum-sulfate treatment, miRNA-146a exhibited the most significant increase in aluminum -treated animals after 5 months (Figures 2A and 2B). [score:1]
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40
[+] score: 19
Other miRNAs from this paper: mmu-mir-9-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-9b-2, mmu-mir-9b-1
Moreover, while the CD11b promoter drives stable and strong expression in CNS macrophages, it is unclear whether miR-9 -based targeting is able to permit transgene expression in transduced microglia under EAE conditions. [score:7]
While the CD11b promoter is active specifically in myeloid cells, the latter are the only CNS cells lacking miR-9, which abolishes expression of transgenic mRNA carrying miR-9 target sequences. [score:5]
Yet miR-9 has been shown to participate in microglial activation [36] and might therefore also block transgene expression following certain activating stimuli. [score:3]
Yao H. Ma R. Yang L. Hu G. Chen X. Duan M. Kook Y. Niu F. Liao K. Fu M. MiR-9 promotes microglial activation by targeting MCPIP1Nat. [score:2]
Apart from this route of administration, specificity for CNS myeloid cells has been accomplished by placing the transduced genes under regulation of e. g., the CD11b promoter [35] or microRNA-9 (miR-9) [34]. [score:2]
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[+] score: 19
The miR-9 acting 3′-untranslated region (UTR) of lamin A suppresses its expression level, thus reducing accumulation of prelamin A, which generates progerin. [score:7]
Future studies on cardiac-specific laminopathy intervention could be focus on inhibiting miR-9 or other cardiac-specific miR targeting on the 3′-UTR of LMNA. [score:5]
The direct role of miR-9 on lamin A gene expression was further confirmed by anti-miR-9 treatment (loss of function) or transfection with pre-miR-9 (gain of function) in the HGPS iPSC-MSC. [score:4]
miR-9 was specifically expressed in neuronal cells derived from HGPS patients, which exerted a protective role of the miR specifically to preserve cognitive function [50]. [score:3]
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[+] score: 18
The results obtained also indicate that although miR-124 and miR-9* are highly expressed in the retina as compared with the mouse platform, they are also expressed in the brain at a similar level. [score:4]
Additionally, retinal preference/specificity was determined for miR-9*, miR-335, miR-31, miR-106, miR-129-3p, miR-691 and miR-26b by microarray analysis, and expression levels of miR-129-3p, miR-335 and miR-31 were also validated using qPCR. [score:3]
In relation to the eye, miR-7 has been shown to play an important role in photoreceptor differentiation in Drosophila [25] and other miRs, such as miR-9, miR-96, miR-124a, miR-181, miR-182, and miR-183, were found to be highly expressed during morphogenesis of the zebrafish eye [16]. [score:3]
Expressions of miR-1, miR-9*, miR-26b, miR-96, miR-129-3p, miR-133, miR-138, miR-181a, miR-182, miR-335 and let7-d were explored by in situ hybridization (ISH) using locked nucleic acid (LNA) probes (Exiqon). [score:3]
For example, miR-9*, miR-335, miR-31, miR-106b, miR-129-3p, miR-691, and miR-26b exhibited a relatively high level of expression in the retina when compared with the brain or the mouse platform. [score:2]
MiR-9* has previously been described as miR-131 [18], but it appears to be the sense strand of all three miR-9 predicted stem-loops. [score:1]
In fact, miR-124 and miR-9* are also known to be brain specific miRs [19, 50, 51]. [score:1]
Previously, miR-9, miR-29c, miR-96, miR-124a, miR-181a, miR-182, miR-183, and miR-204 were localized in the mouse retina by ISH [26- 28]. [score:1]
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[+] score: 17
We also found that predicted targets of miR-128 were significantly down-regulated in the neurons of the auditory and vestibular systems, while the predicted targets of miR-9 were significantly down-regulated only in the neurons of the auditory system. [score:11]
The strength of this approach is further demonstrated by the ability to detect not only compartment specific regulators of cell fate (Zeb1/2, c-Ets1/2, miR-128, miR-9 and miR200b) but also miR-96, a miRNA which is expressed only in a subset of the sensory epithelial cells. [score:4]
Both miR-128 and miR-9 are known to have an important function in neuronal development [16]. [score:2]
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[+] score: 17
Not only does REST downregulate the expression of miR-9 and miR-9*, but miR-9 targets REST and miR-9* targets CoREST, thereby inhibiting the REST silencing complex [90]. [score:12]
Based on these findings, upregulation of miR-9, miR-9*, miR-22, miR-34b, miR-125b, miR-137, miR-146a, miR148a, miR-150, miR-196a, and miR-214 may have therapeutic potential against mutant HTT, REST, HDAC4, apoptosis, and other pathobiological factors in HD. [score:4]
The effects of psychotropics on the other miRNAs listed in Table 2, particularly miR-9, miR-9*, miR-22, miR-34b, miR-125b, miR-137, miR-146a, miR148a, miR-150, miR-196a, and miR-214, as well as on REST, deserve study in HD mo dels. [score:1]
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[+] score: 17
IPost up-regulated miR-1, miR-15b, miR-21, miR-24, miR-26a, miR-27, miR-133a, miR-199a, miR-214, miR-208 and miR-499, while down-regulated miR-23a and miR-9 as compared with Sham group. [score:6]
Compared with sham group, the expressions of miR-1, miR-15b, miR-21, miR-24, miR-26a, miR-27, miR-133a, miR-199a, miR-214, miR-208 and miR-499 were increased in IPost hearts, while miR-9 and miR-23a were down-regulated in IPost mo dels. [score:5]
As previously reported, a collection of miRNAs were abnormally expressed in ischemic mouse hearts in response to I/R injury, such as miR-1, miR-9, miR-15b, miR-21, miR-23a, miR-24, miR-26a, miR-27, miR-133a, miR-199a, miR-208, miR-214 and miR-499 [20, 21, 28]. [score:3]
Then real-time quantitative PCR was performed to quantify the expression level of miR-1, miR-9, miR-15b, miR-21, miR-23a, miR-24, miR-26a, miR-27, miR-133a, miR-199a, miR-208, miR-214 and miR-499 with SYBR Green PCR Master Mix (Applied Biosystems) according to the manufacturer’s instructions. [score:3]
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[+] score: 17
REST directly down-regulates a large number of genes at the transcriptional level, but also probably indirectly activates the expression of other genes at the post-transcriptional level via the repression of many noncoding targets (Conaco et al., 2006; Mortazavi et al., 2006; Wu and Xie, 2006; Visvanathan et al., 2007; Singh et al., 2008; Johnson et al., 2009), including several micro RNAs (miRNAs) considered to be brain-specific (such as miR9, miR124, miR132, miR135, miR139, and miR153; Figure 1). [score:9]
REST regulates the expression of miRNAs and is itself regulated by them, including miR-153 (Mortazavi et al., 2006; Wu and Xie, 2006), miR-9 and miR-29a (Wu and Xie, 2006; Figure 1). [score:5]
Importantly, REST itself appears to be a predicted target of miR-153 (Mortazavi et al., 2006; Wu and Xie, 2006), miR-9 and miR-29a (Wu and Xie, 2006). [score:3]
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[+] score: 17
In females, O [3] exposure induced the expression of miR-301b-3p (log fold change = 1.652), miR-694 (log fold change = 0.727), miR-669 h-3p (log fold change = 0.679), miR-384-5p (log fold change = 0.455), and miR-9-5p (log fold change = 0.378) and downregulated the expression of miR-30d-5p (log fold change = − 0.204) (Fig.   3). [score:8]
O [3] revealed upregulation of both miR-9-5p and miR-130a-3p, which are known for targeting SOCS5 and altering macrophage polarization, respectively [63, 64]. [score:6]
Specifically, we found nine differentially expressed miRNAs in females exposed to O [3] in proestrus: miR-694 (log fold change = 1.492), miR-9-5p (log fold change = 0.836), miR-712-5p (log fold change = 0.667), miR-181d-5p (log fold change = 0.597), miR-98-5p (log fold change = 0.558), miR-200c-3p (log fold change = 0.525), miR-221-3p (log fold change = 0.385), miR-126a-5p (log fold change = 0.421), and miR-106a-5p (log fold change = − 0.527) (Fig.   7). [score:3]
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[+] score: 16
miR-9 is wi dely expressed in neural precursor cells and has lower expression in matured postmitotic neurons [2]. [score:5]
A different review also suggested that overexpression of miR-9 alters migration and proliferation processes of neural precursors [2]. [score:3]
Moreover, miR-9 is expressed in embryonic stem cells during neuronal differentiation [36]. [score:3]
In mammals, miR-9 is a neural-specific miRNA and was not found to be expressed in any other tissues. [score:3]
Importantly, miR-9 regulates neurogenesis at the midbrain-hindbrain boundary in zebrafish brain mo dels [3]. [score:2]
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49
[+] score: 16
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-17, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-134, mmu-mir-137, mmu-mir-138-2, mmu-mir-145a, mmu-mir-24-1, hsa-mir-192, mmu-mir-194-1, mmu-mir-200b, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-215, hsa-mir-221, hsa-mir-200b, mmu-mir-296, mmu-let-7d, mmu-mir-106b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-137, hsa-mir-138-2, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-134, hsa-mir-138-1, hsa-mir-194-1, mmu-mir-192, mmu-mir-200a, 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-24-2, mmu-mir-346, hsa-mir-200c, mmu-mir-17, mmu-mir-25, mmu-mir-200c, mmu-mir-221, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-106b, hsa-mir-200a, hsa-mir-296, hsa-mir-369, hsa-mir-346, mmu-mir-215, gga-let-7i, gga-let-7a-3, gga-let-7b, gga-let-7c, gga-mir-221, gga-mir-17, gga-mir-138-1, gga-mir-124a, gga-mir-194, gga-mir-215, gga-mir-137, gga-mir-7-2, gga-mir-138-2, gga-let-7g, gga-let-7d, gga-let-7f, gga-let-7a-1, gga-mir-200a, gga-mir-200b, gga-mir-124b, gga-let-7a-2, gga-let-7j, gga-let-7k, gga-mir-7-3, gga-mir-7-1, gga-mir-24, gga-mir-7b, gga-mir-9-2, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-192, dre-mir-221, dre-mir-430a-1, dre-mir-430b-1, dre-mir-430c-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-17a-1, dre-mir-17a-2, dre-mir-24-4, dre-mir-24-2, dre-mir-24-3, dre-mir-24-1, dre-mir-25, dre-mir-92b, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-137-1, dre-mir-137-2, dre-mir-138-1, dre-mir-145, dre-mir-194a, dre-mir-194b, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-430c-2, dre-mir-430c-3, dre-mir-430c-4, dre-mir-430c-5, dre-mir-430c-6, dre-mir-430c-7, dre-mir-430c-8, dre-mir-430c-9, dre-mir-430c-10, dre-mir-430c-11, dre-mir-430c-12, dre-mir-430c-13, dre-mir-430c-14, dre-mir-430c-15, dre-mir-430c-16, dre-mir-430c-17, dre-mir-430c-18, dre-mir-430a-2, dre-mir-430a-3, dre-mir-430a-4, dre-mir-430a-5, dre-mir-430a-6, dre-mir-430a-7, dre-mir-430a-8, dre-mir-430a-9, dre-mir-430a-10, dre-mir-430a-11, dre-mir-430a-12, dre-mir-430a-13, dre-mir-430a-14, dre-mir-430a-15, dre-mir-430a-16, dre-mir-430a-17, dre-mir-430a-18, dre-mir-430i-1, dre-mir-430i-2, dre-mir-430i-3, dre-mir-430b-2, dre-mir-430b-3, dre-mir-430b-4, dre-mir-430b-6, dre-mir-430b-7, dre-mir-430b-8, dre-mir-430b-9, dre-mir-430b-10, dre-mir-430b-11, dre-mir-430b-12, dre-mir-430b-13, dre-mir-430b-14, dre-mir-430b-15, dre-mir-430b-16, dre-mir-430b-17, dre-mir-430b-18, dre-mir-430b-5, dre-mir-430b-19, dre-mir-430b-20, mmu-mir-470, hsa-mir-485, hsa-mir-496, dre-let-7j, mmu-mir-485, mmu-mir-543, mmu-mir-369, hsa-mir-92b, gga-mir-9-1, hsa-mir-671, mmu-mir-671, mmu-mir-496a, mmu-mir-92b, hsa-mir-543, gga-mir-124a-2, mmu-mir-145b, mmu-let-7j, mmu-mir-496b, mmu-let-7k, gga-mir-124c, gga-mir-9-3, gga-mir-145, dre-mir-138-2, dre-mir-24b, gga-mir-9-4, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, gga-mir-9b-1, gga-let-7l-1, gga-let-7l-2, gga-mir-9b-2
microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1. [score:5]
MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors. [score:3]
A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. [score:2]
MicroRNAd regulates the TLX/microRNA-9 cascade to control neural cell fate and neurogenesis. [score:2]
MicroRNA-9: functional evolution of a conserved small regulatory RNA. [score:1]
miR-9 is also a brain-enriched miRNA (Landgraf et al., 2007) and it is evolutionary conserved from flies to human (Yuva-Aydemir et al., 2011). [score:1]
miR-9. Conclusion and perspectives. [score:1]
MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. [score:1]
[1 to 20 of 8 sentences]
50
[+] score: 15
In support of the accuracy of the TargetScan algorithm, we found that the Olfr1226 3′ UTR conferred repression in response to exogenously expressed miR-9 (Figure 3B). [score:5]
We found that at least 2 of these miRNAs— miR-9 and -128—are expressed in the OSN layer of the OE (Figure 3A). [score:3]
We functionally tested one of the Olfr 3′ UTRs (Olfr1226) with a predicted miR-9 target site. [score:3]
Zhao C. Sun G. Li S. Shi Y. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination Nat. [score:2]
In situ hybridization In situ hybridization was performed as previously described previously (38) using 10 μm fresh frozen OE cryosections and LNA probes against miR-741, miR-9 and miR-128 (Exigen). [score:1]
In situ hybridization was performed as previously described previously (38) using 10 μm fresh frozen OE cryosections and LNA probes against miR-741, miR-9 and miR-128 (Exigen). [score:1]
[1 to 20 of 6 sentences]
51
[+] score: 15
Since CRE -mediated transcription promotes neuronal plasticity, some up-regulated miRNAs (miR-9, miR-433-3p and miR-26a) may play essential roles in fluoxetine -induced dopaminergic synapse suppression by targeting CREB [67, 68, 69]. [score:8]
For example, miR-9- CREB negative feedback minicircuitry plays a critical role in the determination of proliferation and migration in glioma cells [63, 64]; miR-433-3p suppresses cell growth and enhances chemosensitivity by targeting CREB in human glioma [65]; miR-26a/Kruppel like factor 4 (KLF4) and cAMP responsive element binding protein CCAAT/enhancer binding protein (CREB-C/EBPβ) signaling pathways regulate survival of mycobacterium tuberculosis in macrophages [66]. [score:6]
The well-studied miRNAs within this group included let-7 family (let-7c/d/f/k), miR-212 cluster (miR-212-3p and miR-132-3p/5p), miR-23a/b, miR-9-3p/5p, miR-411 clusters (miR-299a and miR-329) and miR-466 clusters (miR-466m-5p and miR-669f-5p) (Figure 2 and Table 1). [score:1]
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52
[+] score: 14
identified functional, non-canonical regulation globally for miR-128 and miR-124 (Fig. 2), and for individual miR-9, miR-181, miR-30 and miR-125 targets (Fig. 4f and Fig. 8b–m). [score:4]
miRNA mimics repressed most miR-9 (6/7) and miR-181a (5/6) targets examined, including all with canonical seeds and several with seedless interactions and no canonical seed matches in their 3′-UTRs (Fig. 4f). [score:3]
In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis recovered known associations of miR-124, miR-9 and miR-26 with glioma, including known and many novel targets (Supplementary Fig. 4). [score:3]
Gene Ontology analysis indicated neuronal regulatory functions for less-characterized brain miRNAs, including miR-26 (for example, axon development and locomotion), miR-138 (neurotransmitter transport and secretion, and calcium transport) and miR-9* (cell migration and motility; ). [score:1]
miRNA seed sequences for miR-124 and miR-9 are shown below mismatch and miRNA bulge plots. [score:1]
miR-9 was also enriched for seedless binding (k=4, P=2.2 × 10 [−9]). [score:1]
Interestingly, a number of major miRNAs enriched for seedless interactions (for example, miR-9, miR-181, miR-30 and miR-186) have AU-rich seed sites, indicating that weak seed-pairing stability may favour seedless non-canonical interactions 10. [score:1]
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53
[+] score: 14
Assuming that PMP22 is also regulated by miR-9 in Schwann cells, the downregulation of this negative regulator of the major myelin protein PMP22 upon myelination should promote myelin formation. [score:6]
Furthermore, we identified miR-9, miR-455, and miR-1224 as microRNAs downregulated upon myelination and reduced following Dicer ablation from Schwann cells. [score:4]
MiR-9 has previously been shown to regulate PMP22 expression in oligodendrocytes [13]. [score:3]
Only three microRNAs met these criteria: miR-9, miR-455, and miR-1224. [score:1]
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54
[+] score: 14
The bifunctional microRNA miR-9/miR-9 [*] regulates REST and CoREST and is downregulated in Huntington's disease. [score:7]
Alcohol consumption in adult mice leads to an approximately 2-fold increase in the level of miR-9 in the striatum followed by a reduction in expression of a subset of mRNA isoforms that contain miR-9 targets in the 3′ UTR and code for a large conductance calcium and voltage gated potassium channel (Pietrzykowski et al., 2008). [score:5]
Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. [score:2]
[1 to 20 of 3 sentences]
55
[+] score: 14
In the present study, the RT-PCR assay confirmed that miR-155, miR-146a, and miR-9 were aberrantly up-regulated in ApoE knockdown mice. [score:4]
Based on the findings from our previous study that some miRNAs were up-regulated by oxLDL -treated human primary monocytes and on a survey of previously reported miRNA profiling results [10], [17]– [19], five miRNAs (miR-155, miR-146a, miR-125a-5p, miR-29a, and miR-9) were selected in the present study. [score:4]
Some miRNAs (miR-125a-5p, miR-9, miR-146a, miR-29a, and miR-155) were aberrantly expressed after oxLDL treatment. [score:3]
In addition, several other miRNAs (such as miR-146a, miR-29a, and miR-9) are also suggested to be deregulated in AS tissues or CAD patients. [score:2]
No difference was observed in miR-9 and miR-125a-5p. [score:1]
[1 to 20 of 5 sentences]
56
[+] score: 14
As shown in Fig.   2b, miR-132 specifically downregulates the expression of the miR-132 seed containing sensor but not the one containing the miR-9 sequence. [score:6]
The expression of mature miR-132 from the commercial vector (pEZX-MR04 from Gene Copoeia) was validated on the FF-luc reporter constructs containing perfect-match miRNA target-sites for miR-132 and miR-9 (sensors). [score:5]
The perfect seed match sequences for miR-132 or miR-9 were cloned downstream of the firefly luciferase in the FF-luc expressing vector. [score:3]
[1 to 20 of 3 sentences]
57
[+] score: 13
Analysis of mouse retinal miRNA transcriptome [50] reveals that miR-9 is highly expressed in neonatal retina, with peak expression near P10; miR-182 interacts with a photoreceptor-specific cluster of genes and increases expression after P1. [score:7]
Four miRNAs, with established expression and studied function in retinal development, were chosen for analysis, including Let7d, miR-9, miR-182 and miR-204 48– 50. [score:4]
Accordingly, our data reveals that subsets of miRNAs are present in mRPC EVs, including miRNA9, miRNA182, miRNA204 and Let7d. [score:1]
Additionally, the miRNAs identified in EVs included Let7d, miR-9, miR-182 and miR-204. [score:1]
[1 to 20 of 4 sentences]
58
[+] score: 12
Previously, we showed that miRNA targeting of the LGTV genome with a combination of CNS-specific mir-124 and mir-9 targets is more effective for attenuation of virus neurovirulence than is insertion of only mir-124 targets (5). [score:7]
Striped boxes indicate scrambled (synonymous) sequence for mir-124(T) and mir-9(T). [score:1]
IRES-124(4m) was modified by replacing the 5′-terminal copy of the mir-124(T) sequence with that of mir-9(T), generating IRES-124/9(4m). [score:1]
Therefore, we developed an additional virus in which one of the mir-124(T)s was replaced with mir-9(T) [see IRES-124/9(4m) in Fig.  2A]. [score:1]
Red and blue boxes denote mir-124(T) and mir-9(T) sequences, respectively. [score:1]
To generate cap-C, C48-124(2)/9/1-E5 was modified by replacing a sequence for mir-9(T) with mir-124(T) and deleting mir-1(T) in the duplicated C gene region (DCGR). [score:1]
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59
[+] score: 12
Tian J MicroRNA-9 regulates the differentiation and function of myeloid-derived suppressor cells via targeting Runx1J. [score:5]
The transfection of miR-9-5p mimic into c KO AGMs did not change colony counts compared to control mimic -transfected c KO AGMs (Fig.   7e, right), suggesting that the restoration of miR-9-5p and downregulation of Runx1 is not sufficient to rescue HSPC defect in c KO embryos. [score:3]
miR-9-5p is known to target Runx1 [46] and was detectable in HSPCs (Supplementary Table  4). [score:3]
For miR-9-5p, n = Ctr: 7 embryos, c KO: 4 embryos. [score:1]
[1 to 20 of 4 sentences]
60
[+] score: 11
For example, miR-9 was shown to directly target mRNAs of Lif, gp130, and Jak1 by downregulating these crucial upstream elements of the JAK-STAT signaling pathway, thus leading to decreased phosphorylation of STAT and suppression of astrogliogenesis [86]. [score:9]
Therefore, a miR-9 LNA mimic could be developed into a potential therapy to regulate the level of JAK-STAT activation. [score:2]
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61
[+] score: 11
Specific examples include miR-9, which is the most downregulated miRNA in recurrent tumors and is > 1000% higher expressed in undifferentiated 2102Ep cells compared to NTera2, and miR-206, which is in the top ten miRNAs upregulated by recurrent tumors and downregulated during NTera2 differentiation. [score:11]
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62
[+] score: 11
In addition, both miR-128 and miR-9 are highly expressed in the foetal hippocampus and differentially regulated in the normal adult hippocampus as well as the hippocampus of Alzheimer's disease sufferers [50]. [score:6]
We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. [score:3]
MiR-9 regulates the patterning activities and neurogenesis at the midbrain-hindbrain boundary in zebrafish [24] and miR-124 triggers brain-specific alternative pre-mRNA splicing leading to neuronal differentiation in the mouse [25]. [score:2]
[1 to 20 of 3 sentences]
63
[+] score: 11
Accordingly, altered miRNA expression may contribute to CNS pathologies and loss of Dicer and specific miRNAs, including miR-133b and miR-9, has been reported in neurodegenerative diseases [10], [11], [12]. [score:5]
Among other abundant miRNAs were known brain-enriched miRNAs, including miR-9 [38], and miR-132 [8] and astrocyte-expressed miRNAs such as miR-29a [39]. [score:3]
Loss of certain miRNAs has been implicated in neurodegenerative diseases, including miR-9* [48] and miR-106b [49]. [score:3]
[1 to 20 of 3 sentences]
64
[+] 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-19a, hsa-mir-20a, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-30a, hsa-mir-33a, hsa-mir-96, hsa-mir-98, hsa-mir-103a-2, hsa-mir-103a-1, mmu-let-7g, mmu-let-7i, mmu-mir-23b, mmu-mir-30a, mmu-mir-30b, mmu-mir-99b, mmu-mir-125a, mmu-mir-125b-2, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-146a, mmu-mir-155, mmu-mir-182, mmu-mir-183, mmu-mir-24-1, mmu-mir-191, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-181b-1, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-221, hsa-mir-223, hsa-mir-200b, mmu-mir-299a, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-30b, hsa-mir-125b-1, hsa-mir-133a-1, hsa-mir-133a-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-146a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, 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-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-96, mmu-mir-98, mmu-mir-103-1, mmu-mir-103-2, mmu-mir-148b, mmu-mir-351, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, mmu-mir-19a, mmu-mir-25, mmu-mir-200c, mmu-mir-223, mmu-mir-26a-2, mmu-mir-221, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-30c-1, hsa-mir-299, hsa-mir-99b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-361, mmu-mir-361, hsa-mir-365a, mmu-mir-365-1, hsa-mir-365b, hsa-mir-375, mmu-mir-375, hsa-mir-148b, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, mmu-mir-181b-2, mmu-mir-433, hsa-mir-429, mmu-mir-429, mmu-mir-365-2, hsa-mir-433, hsa-mir-490, hsa-mir-193b, hsa-mir-92b, mmu-mir-490, mmu-mir-193b, mmu-mir-92b, hsa-mir-103b-1, hsa-mir-103b-2, mmu-mir-299b, mmu-mir-133c, mmu-let-7j, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-9b-1
With exception of miR-33a, miR223, miR-9, miR-24, and miR-429, whose expression level was low in activated B cells, such Prdm1 -targeting miRNAs were significantly upregulated by HDI. [score:8]
org), we identified miR-125a, miR-125b, miR-96, miR-351, miR-30, miR-182, miR-23a, miR-23b, miR-200b, miR-200c, miR-33a, miR-365, let-7, miR-98, miR-24, miR-9, miR-223, and miR-133 as PRDM1/Prdm1 targeting miRNAs in both the human and the mouse. [score:3]
[1 to 20 of 2 sentences]
65
[+] score: 11
For example, two miRNAs, let-7b and miR-9, inhibit NSC proliferation and promote neuronal differentiation by suppressing Tlx and the oncogenic chromatin regulator Hmga2 [31- 33]. [score:6]
In contrast, miR-9, a miRNA known to be induced by NSPC differentiation [33], was significantly upregulated in differentiating NSPCs. [score:4]
Thus, miR-124, miR-9, and let-7b elicit NSC differentiation, while miR-184 and miR-137 increase proliferation at the expense of differentiation potential. [score:1]
[1 to 20 of 3 sentences]
66
[+] score: 11
Moreover, we detected some other documented oncogenic microRNAs including miR-9 and miR-19a, and tumor suppressing microRNAs including miR-28, miR-33a, miR-34a and miR-214, as well as their targets E-cadherin, PTEN, HoxB3, Pim, KIT and FGFR1, respectively [21– 26], to figure out the Res -induced microRNA expression profile. [score:7]
Here, we also showed that Res did not up-regulate oncogenic miR-9 and miR-19a in HCT-116 cells. [score:4]
[1 to 20 of 2 sentences]
67
[+] score: 11
NF- κB expression is directly affected by miR-9, which inhibits NFKB1 expression [11] and thus NF-κB activity. [score:8]
miR-9 is overexpressed in high grade CaP [46] thus is unlikely to contribute to an increase in NF-κB activation. [score:3]
[1 to 20 of 2 sentences]
68
[+] score: 10
By targeting Onecut2 and Noc2 respectively, miR-9 and miR-96 up-regulate granuphilin, and negatively regulate insulin exocytosis [13, 14]. [score:7]
Oppositely, miR-9 and miR-96 have inhibitory roles in insulin secretion. [score:3]
[1 to 20 of 2 sentences]
69
[+] score: 10
In addition to miR-135a, several CEBPD -downregulated miRNAs including miR-9, miR-19b, miR-29a/b-1, miR-16, and miR-107 were found to be repressed in neurodegenerative diseases [50, 51]. [score:6]
Among them, the expression level of miR-9, miR-29a/b-1, and miR-107 was also reported to be negatively correlated with BACE1 in AD pathogenesis [52– 54]. [score:3]
The attenuation of miR-9 and miR-29a were further found in HD mice, which resulted in the increase of transcription factor REST, a repressor of neurotrophic factor BDNF transcription [31]. [score:1]
[1 to 20 of 3 sentences]
70
[+] score: 10
However, another ethanol-sensitive miRNA, miR-9 (indicated with arrow), is expressed at a higher baseline level compared to miR-153 over -expression. [score:4]
Suppression and epigenetic regulation of MiR-9 contributes to ethanol teratology: evidence from zebrafish and murine fetal neural stem cell mo dels. [score:3]
At this level of expression, miR-153 is 2.5-fold less abundant than miR-9, another ethanol-sensitive miRNA (Balaraman et al., 2012; Pappalardo-Carter et al., 2013; Sathyan et al., 2007). [score:3]
[1 to 20 of 3 sentences]
71
[+] score: 10
Our previous study demonstrated that miR-9 was a regulator in hepatic gluconeogenesis and HPG by directly targeting Foxo1 both in vitro and in vivo [10]. [score:5]
In contrast to miR-139, Gomafu knockdown had no effect on miR-9 expression (Fig.   5B). [score:4]
b The ob/ob mice were injected with si-control, siGomafu-1 or siGomafu-2 daily for 30 days via the tail vein, miR-139 and miR-9 expression was measured. [score:1]
[1 to 20 of 3 sentences]
72
[+] score: 10
Xu et al. [43] showed that the Fragile X protein family member FXR1P regulates the levels of brain-specific miR-9 and miR-124. [score:2]
Furthermore, it has also been reported that miR-9 and miR-124 are abundant in the brain and are involved in brain development [17, 25, 26]. [score:2]
It is noteworthy that analysis displayed no significant difference in miR-9 and miR-124 levels by the VPA exposure. [score:1]
Prenatal exposure to VPA at E12.5 immediately increased miR-132 levels, but not miR-9 or miR-124 levels, in the male embryonic brain. [score:1]
Fig. 1Effects of prenatal VPA exposure at E12.5 on levels of miR-9, miR-124 and miR-132 in the male mouse embryonic whole brain. [score:1]
The VPA exposure caused an approximately 2.5-fold increase in miR-132 levels, but it did not affect the levels of miR-9 or miR-124 (n = 5/group, Fig.   1). [score:1]
We found that prenatal VPA exposure at E12.5 increased miR-132 levels, but not miR-9 or miR-124 levels, in the male mouse embryonic brain. [score:1]
Prenatal VPA exposure at E12.5 increased miR-132 level, but not miR-9 and miR-124 levels, in mouse embryonic brain. [score:1]
[1 to 20 of 8 sentences]
73
[+] score: 9
For the 17 specific miRNAs of the 14d-infected sample, 1954 targets were found in total, with 115 on average; the miRNA that possessed the highest number of targets was mmu-miR-9 (1076 targets), with the best matched target being KEL (Kell blood group, metallo-endopeptidase, NM_000420). [score:9]
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74
[+] score: 9
They also found that the bi-functional brain enriched miR-9/miR-9* targets two components of the REST complex: miR-9 targets REST and miR-9* targets CoREST. [score:7]
Packer et al. (102) used a screen of predicted REST-regulated miRNAs from HD patient brain samples, and found significant decreases of miR-9, miR-9*, and miR-29b as well as a significant increase of miR-132 at late stages. [score:2]
[1 to 20 of 2 sentences]
75
[+] score: 9
Other miRNAs from this paper: mmu-mir-9-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-9b-2, mmu-mir-9b-1
One possibility is that Pax6 expression may be regulated by altered microRNA levels at this stage as it has been shown in neuron progenitor cells microRNA-9 indirectly inhibits Pax6 expression [34]. [score:9]
[1 to 20 of 1 sentences]
76
[+] score: 9
While not discussed in detail in our study, other miRNAs, including miR-124 and miR-9, could also regulate endogenous tau exon 10 splicing in neuronal cells by targeting specific regulatory and/or splicing factors [26]. [score:5]
For instance, downregulation of miR-9 is observed in the presence of exogenous A β in mouse primary neurons [59]. [score:4]
[1 to 20 of 2 sentences]
77
[+] score: 9
The miR-9 control had no effect on the EGFP-Ezh2 3′-UTR expression and the expression of endogenous Ezh2 protein, as expected. [score:5]
miR-26a and miR-101 expression constructs were used as positive controls, and miR-9 was used as a negative control. [score:3]
org, and MicroInspector) or nervous system-specific miRNA miR-9 (41) lacking the predicted binding sites in the Ezh2 3′-UTR. [score:1]
[1 to 20 of 3 sentences]
78
[+] score: 9
As shown in Figure 6A, mRNA targets of several miRNA families were found to be significantly upregulated in hypertrophy (false discovery rate (FDR) <0.05), including those targeted by miR-29, miR-1, miR-9, miR-30, and miR-133. [score:8]
Notably, except for miR-9, these miRNAs are all highly abundant in the heart [17], indicating that our result has the potential to be physiologically relevant. [score:1]
[1 to 20 of 2 sentences]
79
[+] score: 9
The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. [score:7]
An optimized sponge for microRNA miR-9 affects spinal motor neuron development in vivo. [score:2]
[1 to 20 of 2 sentences]
80
[+] score: 8
Other miRNAs from this paper: mmu-mir-9-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-9b-2, mmu-mir-9b-1
Packer et al [34] recently showed that MiR-9, a microRNA that regulates REST expression level, is downregulated in HD and may account for the observed increase of REST expression. [score:8]
[1 to 20 of 1 sentences]
81
[+] score: 8
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-mir-18a, hsa-mir-21, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-30a, hsa-mir-99a, hsa-mir-103a-2, hsa-mir-103a-1, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-30a, mmu-mir-99a, mmu-mir-126a, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-138-2, hsa-mir-192, mmu-mir-204, mmu-mir-122, hsa-mir-204, hsa-mir-1-2, hsa-mir-23b, hsa-mir-122, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-138-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-126, hsa-mir-138-1, mmu-mir-192, mmu-let-7a-1, mmu-let-7a-2, mmu-mir-18a, mmu-mir-21a, mmu-mir-23a, mmu-mir-26a-1, mmu-mir-103-1, mmu-mir-103-2, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-26a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, hsa-mir-26a-2, hsa-mir-376c, hsa-mir-381, mmu-mir-381, mmu-mir-133a-2, rno-let-7a-1, rno-let-7a-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-18a, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-26a, rno-mir-30a, rno-mir-99a, rno-mir-103-2, rno-mir-103-1, rno-mir-122, rno-mir-126a, rno-mir-133a, rno-mir-138-2, rno-mir-138-1, rno-mir-192, rno-mir-204, mmu-mir-411, hsa-mir-451a, mmu-mir-451a, rno-mir-451, hsa-mir-193b, rno-mir-1, mmu-mir-376c, rno-mir-376c, rno-mir-381, hsa-mir-574, hsa-mir-652, hsa-mir-411, bta-mir-26a-2, bta-mir-103-1, bta-mir-16b, bta-mir-18a, bta-mir-21, bta-mir-99a, bta-mir-126, mmu-mir-652, bta-mir-138-2, bta-mir-192, bta-mir-23a, bta-mir-30a, bta-let-7a-1, bta-mir-122, bta-mir-23b, bta-let-7a-2, bta-let-7a-3, bta-mir-103-2, bta-mir-204, mmu-mir-193b, mmu-mir-574, rno-mir-411, rno-mir-652, mmu-mir-1b, hsa-mir-103b-1, hsa-mir-103b-2, bta-mir-1-2, bta-mir-1-1, bta-mir-133a-2, bta-mir-133a-1, bta-mir-138-1, bta-mir-193b, bta-mir-26a-1, bta-mir-381, bta-mir-411a, bta-mir-451, bta-mir-9-1, bta-mir-9-2, bta-mir-376c, bta-mir-1388, rno-mir-9b-3, rno-mir-9b-1, rno-mir-126b, rno-mir-9b-2, hsa-mir-451b, bta-mir-574, bta-mir-652, mmu-mir-21b, mmu-mir-21c, mmu-mir-451b, bta-mir-411b, bta-mir-411c, mmu-mir-126b, rno-mir-193b, mmu-mir-9b-2, mmu-mir-9b-1
Comparison of miRNA expression profiles among tissues revealed that very few miRNAs expression was tissue specific (e. g., miR-9, -124 in brain, miR-122 in liver, miR-1, miR-133a and -206 in muscle). [score:5]
Our comparison of miRNA expression across 11 tissues from bovine revealed a few tissue specific miRNAs: miR-9, -124 in brain, miR-122 in liver, miR-1, miR-133a and -206 in muscle, which had been previously reported in mouse and human [13, 27]. [score:3]
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82
[+] score: 8
Other miRNAs from this paper: hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-23a, hsa-mir-100, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, mmu-mir-1a-1, mmu-mir-23b, mmu-mir-125b-2, mmu-mir-130a, mmu-mir-9-2, mmu-mir-145a, mmu-mir-181a-2, mmu-mir-184, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-205, mmu-mir-206, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-199a-2, hsa-mir-205, hsa-mir-181a-1, hsa-mir-214, hsa-mir-219a-1, hsa-mir-223, mmu-mir-302a, hsa-mir-1-2, hsa-mir-23b, hsa-mir-125b-1, hsa-mir-130a, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125b-2, hsa-mir-184, hsa-mir-206, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-21a, mmu-mir-23a, mmu-mir-103-1, mmu-mir-103-2, rno-mir-338, mmu-mir-338, rno-mir-20a, hsa-mir-1-1, mmu-mir-1a-2, hsa-mir-181b-2, mmu-mir-107, mmu-mir-17, mmu-mir-100, mmu-mir-181a-1, mmu-mir-214, mmu-mir-219a-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-181b-1, mmu-mir-125b-1, hsa-mir-302a, hsa-mir-219a-2, mmu-mir-219a-2, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-367, hsa-mir-372, hsa-mir-338, mmu-mir-181b-2, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-23a, rno-mir-23b, rno-mir-100, rno-mir-103-2, rno-mir-103-1, rno-mir-107, rno-mir-125b-1, rno-mir-125b-2, rno-mir-130a, rno-mir-145, rno-mir-181a-2, rno-mir-181b-1, rno-mir-181b-2, rno-mir-184, rno-mir-199a, rno-mir-205, rno-mir-206, rno-mir-181a-1, rno-mir-214, rno-mir-219a-1, rno-mir-219a-2, rno-mir-223, hsa-mir-512-1, hsa-mir-512-2, rno-mir-1, mmu-mir-367, mmu-mir-302b, mmu-mir-302c, mmu-mir-302d, rno-mir-17-2, hsa-mir-1183, mmu-mir-1b, hsa-mir-302e, hsa-mir-302f, hsa-mir-103b-1, hsa-mir-103b-2, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-219b, hsa-mir-23c, hsa-mir-219b, mmu-mir-145b, mmu-mir-21b, mmu-mir-21c, mmu-mir-219b, mmu-mir-219c, mmu-mir-9b-2, mmu-mir-9b-1
For instance, a study analyzing miRNA expression profiles of ovarian adenocarcinomas demonstrated that two similarly expressed miRNAs (miR-9 and miR-223) regulate two independent targets of a common pathway involved in ovarian metastatis [38]. [score:8]
[1 to 20 of 1 sentences]
83
[+] score: 8
No suppression was seen after cotransfection with a negative control vector expressing miR-9 [31], which has no predicted binding site in hPGRN mRNA (Fig. 2C). [score:5]
Transfection of miR-29b but not miR-9 mimics decreased luciferase reporter expression (Fig. 2D). [score:3]
[1 to 20 of 2 sentences]
84
[+] score: 8
In E16.5 control mice, while miRNAs Let-7a and miR-9 were highly expressed in the cortex and the hippocampus, their expression was undetectable in Emx1-Dicer cko brains (Fig. 2A, B). [score:5]
Similarly, Let-7a and miR-9 expression was depleted in the E14.5 Nestin-Dicer cko cortex and hippocampus, and was greatly reduced in the P22 Nex-Dicer cko hippocampus (Fig. 2C–F). [score:3]
[1 to 20 of 2 sentences]
85
[+] score: 8
For instance, the induction of transcription of miR-146a or miR-9 by LPS, tumor necrosis factor alpha (TNFα) and IL-1α is dependent on NF-κB, and in turn, miR-146a potentially targets TRAF6 and IRAK-1, whereas miR-9 targets the NFkB1 transcript, dampening the immune response (Bazzoni et al., 2009; Quinn and O’Neill, 2011). [score:5]
Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. [score:2]
In particular, miR-155, miR-21, miR-146a, miR-132, miR-9, and miR-147 have all been significantly implicated in the immune response initiated by IL-1R or TLRs (Bazzoni et al., 2009; Nahid et al., 2011; Quinn and O’Neill, 2011). [score:1]
[1 to 20 of 3 sentences]
86
[+] score: 8
Among these microRNAs, miR-204, miR-9, miR-142-3p and miR-199a-5p have been experimentally shown to downregulate Sirt1 (refs 14, 15, 16). [score:4]
Among the microRNAs downregulated by nCounter array in GFM aortas (Supplementary Fig. 2d), miR-204 and miR-148a were confirmed by quantitative PCR (qPCR), with a strong trend for miR-9 (Supplementary Fig. 2e). [score:4]
[1 to 20 of 2 sentences]
87
[+] score: 8
The extracellular calcium concentration is first sensed by the calcium sensing receptor (CaSR) expressed in the basolateral membrane of TALH cells (56); CaSR then regulates the transcription levels of two microRNA genes, miR-9 and miR-374 through nuclear factor of activated T-cells (NFAT) binding and histone deacetylation (52, 55); the transcribed microRNA molecules recognize the partially complementary binding sites in the 3′-UTR region of the claudin-14 mRNA, suppress its protein translation and reduce its stability (51). [score:8]
[1 to 20 of 1 sentences]
88
[+] score: 7
This phenomenon includes an intricate network formed by the ability of let-7d and mir-9 to silence Nr2e1 expression by binding the 3′ UTR regions of this gene and the ability of Nr2e1 to inactivate the expression of mir-9 in a first feedback loop [22, 24]. [score:5]
Second, the balance between NSC proliferation and differentiation has been demonstrated to be under the control of regulatory loops involving both Nr2e1, and microRNA encoding genes such as mir-9, miR-137, and let-7d [22– 24]. [score:2]
[1 to 20 of 2 sentences]
89
[+] score: 7
We found that silencing of TALNEC2 in U87 cells resulted in an increased expression of miRNAs associated with tumor suppression [38, 39] (e. g., let-7b, miR-7, miR-124, miR-137, miR-129-3p, miR-142-3p, miR-205, miR-376c, miR-492, miR-562 and miR-3144) and in a decrease in the expression of miRNAs associated with tumor promotion [38– 40] (e. g., miR-9, miR-21 miR-33b, miR-155, miR-191, miR-525-3p, and miR-767-3p). [score:7]
[1 to 20 of 1 sentences]
90
[+] score: 7
Conversely, miR-9 was among the most expressed miRNAs in miRNA-Seq data but poorly detected by microarrays. [score:3]
For example, acute stress increases let-7a, miR-9 and miR-26a/b expression levels in the mouse frontal cortex (FCx), but not in the hippocampus (HP) [8], and miR-212 signalling in the rat striatum has a role in determining vulnerability to cocaine addiction [9]. [score:3]
These differences might be partly attributed to the multi-organism probe content on the Affymetrix array, as miR-709 is represented by mouse-specific probe sets, while miR-9 has similar probe sets for 23 different organisms, all of which were called “present” in our dataset. [score:1]
[1 to 20 of 3 sentences]
91
[+] score: 7
For example, stem cell specific miRNAs of the miR-290 family (miR-291–295, [24]) were detected to be about 25-fold overexpressed in mouse embryonic stem cells, while brain-specific miR-124 and miR-9 were about 14-fold overexpressed in mouse brain (Supplementary Table  2). [score:5]
Analysis of the results showed that neural miRNAs such as miR-9 and miR-9* were well detected (Figure 1(a)) in contrast to snoRNAs which were almost undetectable (Figure 1(b)). [score:1]
Moreover, almost all antisense snoRNA capture probes detected their specific snoRNA but with different intensities (Figure 4(b)), while the detection levels of miR-9 and miR-9* remained identical (Figure 4(c)). [score:1]
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92
[+] score: 7
For example, miR-208, miR-9, let-7a, 7b, and miR-22* were found to be up-regulated in transformed IEC-6 cells, whereas miR-539, miR-181d, and miR-146a were down-regulated. [score:7]
[1 to 20 of 1 sentences]
93
[+] score: 7
Four of the six most highly expressed of these miRNAs were not differentially regulated and were among the top 25 most expressed miRNAs in the neuronal cultures (mmu-miR-137, mmu-miR-9*, mmu-miR-17, mmu-miR-30c). [score:6]
Many of the miRNAs that were previously linked to neuronal biology (e. g. mmu-miR-124, mmu-miR-125 family, mmu-miR-137, mmu-miR-128, mmu-miR-9 and mmu-let-7) [6, 25- 32, 57, 58] belong to this category. [score:1]
[1 to 20 of 2 sentences]
94
[+] score: 7
Packer A. N. Xing Y. Harper S. Q. Jones L. Davidson B. L. The Bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease J. Neurosci. [score:7]
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95
[+] score: 7
Expression levels are normalized on miR-9 and plotted as 2 [∧−ΔCt] values, according to qRT-PCR expression data. [score:5]
TaqMan quantitative real-time PCR was performed with hsa-miR-16, hsa-let7a, hsa-miR-125b, mmu-miR93, mmu-miR-124a, hsa-miR-23a, hsa-miR-106b, hsa-miR-25 and hsa-miR-9 specific probes (Life Technologies-Applied Biosystems) on ABI7900 thermal cycler. [score:1]
Data were normalized on miR-9 expression level and the fold change to stem/precursors values was calculated trough ΔΔCt method. [score:1]
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96
[+] score: 7
Of these, 12 (mir-9, mir-200c, mir-708, mir-377, mir-26b, mir-296, mir-369, mir-32, mir-1965, mir-1190, mir-135b and mir-201) were differentially up-regulated and five (mir-291a, mir-190b, mir-297c, mir-713 and mir-470) were differentially down-regulated. [score:7]
[1 to 20 of 1 sentences]
97
[+] score: 7
To discover if the up regulation of the BART miRNAs was specific to the viral miRNAs or represented a more general phenomenon we first examined the expression of three cellular miRNAs mir-9, mir-34a and mir-26a. [score:4]
However, these changes were not consistent (mir-9 was mostly highly expressed in the NPC explants) and did not always achieve statistical significance. [score:3]
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98
[+] score: 7
The majority of miRNAs that showed Aire dependency in cell culture were either not expressed in TECs or expressed at similar levels in TECs and T cells with two exceptions; miR-200b, which was TEC specific, but not maturation dependent, and miR-9, which was only expressed in mature mTECs in the mouse, but not in human. [score:7]
[1 to 20 of 1 sentences]
99
[+] score: 6
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-22, hsa-mir-28, hsa-mir-29b-1, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-1a-1, mmu-mir-29b-1, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-133a-1, mmu-mir-145a, mmu-mir-150, mmu-mir-10b, mmu-mir-195a, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-206, mmu-mir-143, hsa-mir-10a, hsa-mir-10b, hsa-mir-199a-2, hsa-mir-217, hsa-mir-218-1, hsa-mir-223, hsa-mir-200b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-150, hsa-mir-195, hsa-mir-206, mmu-mir-200a, 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-16-1, mmu-mir-16-2, mmu-mir-21a, mmu-mir-22, mmu-mir-29c, rno-let-7d, rno-mir-329, mmu-mir-329, rno-mir-331, mmu-mir-331, rno-mir-148b, mmu-mir-148b, rno-mir-135b, mmu-mir-135b, hsa-mir-200c, hsa-mir-1-1, mmu-mir-1a-2, mmu-mir-10a, mmu-mir-17, mmu-mir-28a, mmu-mir-200c, mmu-mir-218-1, mmu-mir-223, mmu-mir-199a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7b, mmu-mir-217, hsa-mir-29c, hsa-mir-200a, hsa-mir-365a, mmu-mir-365-1, hsa-mir-365b, hsa-mir-135b, hsa-mir-148b, hsa-mir-331, mmu-mir-133a-2, mmu-mir-133b, hsa-mir-133b, 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-7b, rno-mir-9a-1, rno-mir-9a-3, rno-mir-9a-2, rno-mir-10a, rno-mir-10b, rno-mir-16, rno-mir-17-1, rno-mir-21, rno-mir-22, rno-mir-28, rno-mir-29b-1, rno-mir-29c-1, rno-mir-124-3, rno-mir-124-1, rno-mir-124-2, rno-mir-133a, rno-mir-143, rno-mir-145, rno-mir-150, rno-mir-195, rno-mir-199a, rno-mir-200c, rno-mir-200a, rno-mir-200b, rno-mir-206, rno-mir-217, rno-mir-223, dre-mir-7b, dre-mir-10a, dre-mir-10b-1, dre-mir-217, dre-mir-223, hsa-mir-429, mmu-mir-429, rno-mir-429, mmu-mir-365-2, rno-mir-365, dre-mir-429a, hsa-mir-329-1, hsa-mir-329-2, hsa-mir-451a, mmu-mir-451a, rno-mir-451, dre-mir-451, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-1-2, dre-mir-1-1, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-10b-2, dre-mir-16a, dre-mir-16b, dre-mir-16c, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-22a, dre-mir-22b, dre-mir-29b-1, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-133a-2, dre-mir-133a-1, dre-mir-133b, dre-mir-133c, dre-mir-143, dre-mir-145, dre-mir-150, dre-mir-200a, dre-mir-200b, dre-mir-200c, dre-mir-206-1, dre-mir-206-2, dre-mir-365-1, dre-mir-365-2, dre-mir-365-3, dre-let-7j, dre-mir-135b, rno-mir-1, rno-mir-133b, rno-mir-17-2, mmu-mir-1b, dre-mir-429b, rno-mir-9b-3, rno-mir-9b-1, rno-mir-9b-2, rno-mir-133c, mmu-mir-28c, mmu-mir-28b, hsa-mir-451b, mmu-mir-195b, mmu-mir-133c, mmu-mir-145b, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-mir-451b, mmu-let-7k, rno-let-7g, rno-mir-29c-2, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1
In them, four miRNAs (miR-9, miR-124, miR-128a and miR-128b) were previously reported to be specifically expressed in the cortex and hippocampus in rat [18]. [score:3]
Moreover, miR-200b is enriched in zebrafish olfactory bulb; miR-124 and miR-9 expression are detected throughout adult brain [16]. [score:3]
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100
[+] score: 6
Recently, several miRNAs including miR-181a and b, miR-9, miR-204, miR-199b, and miR-135a were shown to down-regulate SIRT1 expression in mESC [22]. [score:6]
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