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13 publications mentioning hsa-mir-1296

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-1296. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

1
[+] score: 512
Other miRNAs from this paper: hsa-mir-1297
Western blot and IF results showed that miR-1296 overexpression increased the expression epithelial marker E-cadherin and inhibited the levels of mesenchymal marker N-cadherin and Vimentin in HCCLM3 cells (P < 0.05, respectively, Fig. 3a and b). [score:7]
Moreover, we found the expressions of SRPK1 in the miR-1296 high -expressing tumors were significantly lower than those in the miR-1296 low -expressing tumors (P < 0.05, respectively, Fig. 4e- g). [score:7]
e and f The expression of SRPK1 in miR-1296 high -expressing tumors was significantly lower than that in miR-1296 low -expressing tumors, as determined by qRT-PCR and immunoblotting. [score:7]
Moreover, Kaplan-Meier survival curves suggested that miR-1296 low expressing HCC patients showed a notably reduced overall survival (OS) and disease-free survival (DFS), while SRPK1 high expressing patients conferred an obviously poorer OS and DFS (P < 0.05, respectively, Fig. 7a- d). [score:7]
The 3′-UTR sequence of SRPK1 predicted to interact with miR-1296, together with a corresponding mutated sequence within the predicted target sites, were synthesized and inserted into the pmiR-GLO dual-luciferase miRNA target expression vector (Promega, Madison, WI, USA) called wt-SRPK1 3′-UTR and mt-SRPK1 3′-UTR. [score:7]
Conversely, the expression of Vimentin in the miR-1296 high expression group was markedly lower than that in low expression group (P < 0.05, Fig. 3e and Additional file 2: Figure S2). [score:7]
Moreover, we also found that the miR-1296 high expressing HCC tissues showed increased expression of E-cadherin and decreased expression of Vimentin. [score:7]
We found that E-cadherin expression in miR-1296 high expressing HCC tissues was notably higher than that in low expressing cases (P < 0.05, Fig. 3e and Additional file 2: Figure S2). [score:7]
The activator of PI3K/AKT pathway abrogated the inhibitory effect of miR-1296, while AKT inhibitor reversed the promoting effects of miR-1296 knockdown on migration, invasion and EMT process of HCC cells. [score:6]
However, modulating miR-1296 expression in HCC cells didn’t affect the levels of ERBB2, CCND1 and MCM2 protein, which were confirmed as direct targets of miR-1296 in other tumors (Additional file 3: Figure S3). [score:6]
In contrast, miR-1296 knockdown decreased E-cadherin expression and increased N-cadherin and Vimentin expression in Hep3B cells (P < 0.05, respectively, Fig. 3c and d). [score:6]
To confirm this hypothesis, we performed qRT-PCR and and found that ectopic expression of miR-1296 dramatically decreased, whereas miR-1296 knockdown increased the expressions of SRPK1 mRNA and protein in HCC cells (P < 0.05, respectively, Fig. 4b and c). [score:6]
a and b Overall survival (OS) and disease-free survival (DFS) were compared between miR-1296 high expressing HCC patients and low expressing cases. [score:6]
Taken together, these data suggest that miR-1296 inhibits metastatic behaviors of HCC and regulates SRPK1 expression in vivo. [score:6]
In this study, gain- and loss-of-function experiment confirmed that miR-1296 overexpression inhibited the migration and invasion of HCC cells while miR-1296 knockdown increased these metastatic behaviors in vitro and in vivo. [score:6]
Furthermore, we confirm that miR-1296 inhibits migration, invasion and EMT process of HCC cells probably by directly targeting SRPK1 -mediated PI3K/AKT pathway. [score:6]
miR-1296 does not regulate the expression of other predicted targets in HCC cells. [score:6]
c miR-1296 overexpression reduced the expression of SRPK1 protein in HCCLM3 cells and miR-1296 knockdown increased the level of SRPK1 protein in Hep3B cells. [score:6]
These results suggest that miR-1296 inhibits HCC metastasis by suppressing EMT phenotype. [score:5]
MiRNA vectors, including precursor miR-1296 clones (HmiR0471), precursor miR-1296 scrambled control clones (miR-control; CmiR0001), miR-1296 inhibitors (anti-miR-1296; HmiR-AN0143) and miR-1296 inhibitor control clones (anti-miR-NC; CmiR-AN0001) were obtained from Genecopoeia (Guangzhou, China). [score:5]
Hypoxia condition significantly increased HIF-1α expression in Hep3B cells (P < 0.05, Fig. 9a) and led to a decrease of miR-1296 expression (P < 0.05, Fig. 9b). [score:5]
To confirm that SRPK1 is a functional mediator of miR-1296, SRPK1 was restored by overexpression plasmids in miR-1296 -overexpressing HCCLM3 cells (P < 0.05, Fig. 5a). [score:5]
g Representative immunohistochemical staining showed a weak staining of SRPK1 in miR-1296 high -expressing HCC tissue and strong staining of SRPK1 in the miR-1296 low -expressing tumor. [score:5]
In addition, the miR-1296 expression was significantly down-regulated in all HCC cell lines as compared with normal hepatic cell line LO2 (P < 0.05, respectively, Fig. 1d). [score:5]
As shown in Table 1, we found that underexpression of miR-1296 was significantly associated with tumor-node-metastasis (TNM) stage (III + IV, P = 0.011), venous invasion (P = 0.024) and multiple tumor nodes (P = 0.012), while SRPK1 overexpression was correlated with venous invasion (P = 0.006) and advanced TNM stage (P = 0.001). [score:5]
e SRPK1 restoration decreased the expression of E-cadherin and increased the levels of N-cadherin and Vimentin in miR-1296 overexpressing HCCLM3 cells. [score:5]
Next, transwell assays revealed that miR-1296 overexpression significantly inhibited the migration and invasion of HCCLM3 cells (P < 0.05, respectively, Fig. 2c), whereas miR-1296 knockdown obviously increased the number of migrated and invaded Hep3B cells (P < 0.05, respectively, Fig. 2d). [score:5]
Notably, miR-1296 underexpression, SRPK1 overexpression and their combination are potential prognostic predictors for the survival of HCC patients. [score:5]
A mechanism by which miR-1296 inhibits EMT and metastasis probably by targeting SRPK1 -mediated PI3K/AKT pathway plays an important role in this process. [score:5]
a miR-1296 -overexpressing HCCLM3 cells that were transfected with empty vector (EV) or SRPK1 overexpression plasmid were subjected to western blot for SRPK1. [score:5]
Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. [score:5]
In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. [score:5]
b HCCLM3 and Hep3B cells that were transfected with precursor miR-1296 and miR-1296 inhibitors (anti-miR-1296), respectively, were subjected to qRT-PCR for SRPK1 mRNA expression. [score:5]
Moreover, we also demonstrated that lung sections of miR-1296 overexpression group in fact showed decreased expression of SRPK1 (P < 0.05, Fig. 6b). [score:5]
In addition, we confirmed that miR-1296 underexpression and SRPK1 overexpression as well as their combination were obviously correlated with poor prognosis of HCC patients. [score:5]
In conclusion, we demonstrate for the first time that miR-1296 is underexpressed in HCC tissues and cell lines, and its reduced expression is correlated with malignant clinicopathological features. [score:5]
d miR-1296 overexpression significantly suppressed, while miR-1296 loss increased the luciferase activity that carried wild-type (wt) but not mutant (mt) 3′-UTR of SRPK1. [score:5]
Notably, serine-arginine protein kinase 1 (SRPK1) was identified as a direct target of miR-1296 and mediated the function of miR-1296 in HCC cells. [score:4]
Fig. 4SRPK1 is a direct target of miR-1296 in HCC cells. [score:4]
In contrary, miR-1296 knockdown in Hep3B cells led to a significant increased lung metastasis nodules and SRPK1 expression (P < 0.05, Fig. 6c and d). [score:4]
Similarly, SRPK1 knockdown by a specific siRNA in miR-1296-suppressive Hep3B cells significantly reversed the promoting function induced by miR-1296 loss on Hep3B cell migration and invasion (P < 0.05, respectively, Fig. 5c and d). [score:4]
As shown in Fig. 8a, miR-1296 overexpression significantly decreased, while miR-1296 knockdown increased the level of phosphorylated AKT in HCC cells (P < 0.05, respectively). [score:4]
c miR-1296 knockdown decreased E-cadherin expression, and increased the levels of N-cadherin and Vimentin in Hep3B cells. [score:4]
miR-1296 is down-regulated in hypoxia condition and mediates the effects of hypoxia on HCC metastasis. [score:4]
Notably, SRPK1, a direct downstream target of miR-1296 in this study, is elevated at mRNA and protein level in hypoxia condition [28]. [score:4]
e Immunohistochemistry of E-cadherin and Vimentin were showed and compared between miR-1296 high expressing HCC tissues and miR-1296 low expressing cases. [score:4]
Here, we confirmed that SRPK1 was a direct downstream target of miR-1296 and mediated the biological function of miR-1296 in HCC. [score:4]
In this research, we found that miR-1296 was significantly down-regulated in HCC tissues and cell lines for the first time. [score:4]
SRPK1 is a direct target of miR-1296 in HCC. [score:4]
In summary, the deregulation of miR-1296 may play an important role in tumor metastasis and may be a novel prognostic factor and potential therapeutic target for HCC. [score:4]
Further experiments were performed to disclose whether miR-1296 inhibited HCC metastasis via regulating EMT. [score:4]
Zhu et al. demonstrated that miR-1296 was involved in the regulation of cell migration and invasion in human gastric cancer via targeting ERBB2/Rac1 signaling pathway [14]. [score:4]
In addition, miR-1296 upregulation could serve as a predictive marker for the colon cancer cases with subsequent relapse [17], which indicates that miR-1296 serves as an oncogene in colon cancer. [score:4]
To conclude, we recognize miR-1296 underexpression as a biomarker for predicting poor prognosis of HCC patients. [score:3]
b IF staining of E-cadherin and Vimentin after miR-1296 overexpression in HCCLM3 cells. [score:3]
Underexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. [score:3]
In addition, we further explored the correlation between the expression of miR-1296 and EMT markers in HCC tissues. [score:3]
Reduced miR-1296 expression confers metastasis and recurrence of HCC. [score:3]
c AKT inhibitor MK2206 treatment abrogated the effect of miR-1296 loss on mobility of Hep3B cells. [score:3]
Either SRPK1 re -expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. [score:3]
We found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. [score:3]
b IGF-1 treatment promoted the migration and invasion of miR-1296 overexpressing HCCLM3 cells. [score:3]
The expression of miR-1296 in HCC tissues was significantly lower than that in matched adjacent non-tumor tissues (P < 0.05, Fig. 1a). [score:3]
MiR-1296 overexpression or knockdown accordingly altered the luciferase activity of wt 3’UTR but not mt 3’UTR of SRPK1. [score:3]
But modulating miR-1296 expression showed no significant effect on the luciferase activity of mutant (mt) SRPK1 3′-UTR (Fig. 4d). [score:3]
a of epithelial marker E-cadherin, and mesenchymal markers N-cadherin and Vimentin after miR-1296 overexpression in HCCLM3 cells. [score:3]
We found that IGF-1 treatment at least partially rescued the miR-1296 -induced inhibition of cell migration and invasion (P < 0.05, respectively, Fig. 8b). [score:3]
These data indicate that aberrant expressions of miR-1296 and SRPK1 is correlated with poor prognostic features of HCC patients. [score:3]
Representative IHC results indicated that strong staining of E-cadherin and weak staining of Vimentin and SRPK1 were observed in miR-1296 high -expressing HCC tissue. [score:3]
In present study, we demonstrated that miR-1296 suppressed EMT events of HCC cells. [score:3]
Moreover, miR-1296 was down-regulated in tumor tissues from patients with recurrence compared to patients without recurrence (P < 0.05, Fig. 1c). [score:3]
Here, we found that both low expression of miR-1296 and high level of SRPK1 were significantly associated with adverse clinical features of HCC patients. [score:3]
We determine the expression level of miR-1296 in 50 pairs of randomly selected tumor tissues and matched adjacent non-tumor tissues. [score:3]
Next, we treated miR-1296 -overexpressing HCCLM3 cells with insulin-like growth factor 1 (IGF-1), which was an activator of PI3K/AKT pathway. [score:3]
Moreover, hypoxia is a key cause for miR-1296 underexpression in HCC cells. [score:3]
Weak staining of E-cadherin and strong staining of Vimentin and SRPK1 were presented in miR-1296 low -expressing HCC tissues. [score:3]
Moreover, the aggressive and recurrent phenotype of HCC showed a lower expression of miR-1296. [score:3]
These data indicate that miR-1296 plays a tumor suppressive role in HCC. [score:3]
miR-1296 inhibits EMT process of HCC cells. [score:3]
miR-1296 inhibits HCC cell migration and invasion in vitro. [score:3]
These data suggest that miR-1296 plays a tumor suppressive role in malignancies. [score:3]
Taken together, the expression level and biological function of miR-1296 is cancer-specific. [score:3]
b Immunohistochemistry suggested that SRPK1 expression showed a weaker staining in HCCLM3-miR-1296 cells than control cells. [score:3]
a HCCLM3 and Hep3B cells that were transfected with corresponding miRNA vectors were subjected to qRT-PCR for miR-1296 expression. [score:3]
miR-1296 suppresses EMT process of HCC cells. [score:3]
Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. [score:3]
With combination analysis, the data showed that patients with low miR-1296 and high SRPK1 expression had the worst OS and DFS (P < 0.05, respectively, Fig. 7e and f). [score:3]
d Immunohistochemistry revealed that SRPK1 expression in shows a stronger staining in Hep3B-anti-miR-1296 cells than control cells. [score:3]
These data demonstrated that SRPK1 is not only a downstream target, but also a functional mediator of miR-1296 in HCC. [score:3]
Therefore, reduced expression of miR-1296 is probably correlated with metastasis and recurrence of HCC. [score:3]
c miR-1296-suppressive Hep3B cells that were transfected with scrambled siRNA or SRPK1 siRNA were subjected to western blot for SRPK1. [score:3]
However, the expression and role of miR-1296 in HCC remain unknown. [score:3]
Furthermore, modulating SPRK1 expression mediated the effects of miR-1296 on EMT events in HCC cells (P < 0.05, respectively, Fig. 5e and f). [score:3]
Comparing differences in the expressions of miR-1296 between (a) HCC and matched tumor-adjacent tissues; (b) aggressive and nonaggressive tumor tissues; (c) HCC tissues arising from recurrent and non-recurrent groups; and (d) HCC cell lines and the immortalized hepatic cell line LO2. [score:3]
Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. [score:3]
Third, miR-1296 was inversely correlated with the expressions of SRPK1 in HCC tissues. [score:3]
Taken together, these results suggest that miR-1296 suppresses EMT process of HCC cells. [score:3]
Our results showed that underexpression of miR-1296 was associated with poor prognostic features of HCC patients. [score:3]
SRPK1 restoration abrogated the inhibitory effects of miR-1296 on migration and invasion of HCCLM3 cells (P < 0.05, respectively, Fig. 5b). [score:3]
These data indicate that miR-1296 suppresses the activation of PI3K/AKT pathway in HCC cells. [score:3]
b SRPK1 restoration promoted migration and invasion of miR-1296 -overexpressing HCCLM3 cells. [score:3]
Our data showed that miR-1296 expression was significantly decreased in hypoxia. [score:3]
We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. [score:3]
Interestingly, miR-1296 overexpression abolished the promoting effects of hypoxia on migration and invasion of Hep3B cells (P < 0.05, Fig. 9c). [score:3]
Hypoxia -induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway. [score:3]
c Cell migration and invasion as measured by Transwell assays were inhibited by miR-1296 overexpression in HCCLM3 cells. [score:2]
Firstly, we assessed cell growth by MTT assays and no significant difference was observed after modulating miR-1296 expression in HCC cells (Fig. 2b). [score:2]
d IF staining of E-cadherin and Vimentin after miR-1296 knockdown in Hep3B cells. [score:2]
d SRPK1 knockdown abrogated the effects of miR-1296 loss on migration and invasion of Hep3B cells. [score:2]
Conversely, the restraint of the PI3K/AKT pathway by MK2206 abrogated the effects of miR-1296 knockdown on Hep3B cell migration and invasion (P < 0.05, respectively, Fig. 8c). [score:2]
In contrast, miR-1296 knockdown increased the luciferase activity of wt SRPK1 3′-UTR (P < 0.05, Fig. 4d). [score:2]
c Transwell assays revealed that hypoxia promoted migration and invasion of Hep3B cells, while miR-1296 overexpression abolished the effects of hypoxia. [score:2]
MiR-1296, a novel cancer-related miRNA, has been found to be dysregulated in cancers [11– 13]. [score:2]
f SRPK1 knockdown abolished the effects of miR-1296 loss on EMT process of Hep3B cells. [score:2]
Thus, our results demonstrate that PI3K/AKT signaling functions in miR-1296-regulated HCC cell mobility and EMT. [score:2]
These results suggest that miR-1296 regulates HCC cell migration and invasion. [score:2]
Thus, we hypothesized that the miR-1296-SRPK1 axis could be regulated by hypoxia. [score:2]
d miR-1296 knockdown promoted migration and invasion of Hep3B cells. [score:2]
Next, luciferase reporter assay confirmed that miR-1296 overexpression significantly decreased the luciferase activity of wild-type (wt) SRPK1 3′-UTR (P < 0.05, Fig. 4d). [score:2]
The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay. [score:2]
First, miR-1296 negatively regulated SRPK1 abundance in HCC cells. [score:2]
MiR-1296 inhibited migration, invasion and EMT progression of HCC cells in vitro and in vivo. [score:2]
Moreover, modulating activation of PI3K/AKT pathway reversed the regulatory effects of miR-1296 on EMT events of HCC cells (P < 0.05, respectively, Fig. 8d). [score:2]
As measured by qRT-PCR, we confirmed that miR-1296 was effectively overexpressed in HCCLM3 cells while knocked down in Hep3B cells (P < 0.05, Fig. 2a). [score:2]
b Modulating miR-1296 expression showed no obvious effect on proliferation of HCC cells, as determined by MTT assays. [score:2]
Fig. 5Modulation of SRPK1 partially abolishes miR-1296 -mediated cellular processes in HCC. [score:1]
The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. [score:1]
Nevertheless, the function of miR-1296 and its underlying molecular mechanisms in HCC remain unknown. [score:1]
And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296. [score:1]
For each cohort, subgroups were divided according to the cutoff values, which were determined as the median level of miR-1296 and SRPK1 in HCC tissues. [score:1]
The prognostic significance of miR-1296 and SRPK1 in another cohort of HCC patients. [score:1]
It’s necessary to confirm whether miR-1296 and SRPK1 could serve as valuable biomarkers for diagnosis and prognostic prediction. [score:1]
Similarly, the positive effects of hypoxia on EMT process were reversed by miR-1296 restoration in Hep3B cells (P < 0.05, Fig. 9d). [score:1]
The results showed that miR-1296 overexpression group showed fewer and smaller foci in the lungs of nude mice via microscopic evaluation (P < 0.05, Fig. 6a). [score:1]
c Representative HE staining of lung metastases between Hep3B-anti-miR-1296 cells and control cells. [score:1]
Therefore, we tried to explore the relationship between hypoxia and miR-1296 in HCC. [score:1]
PI3K/AKT signaling is essential for the biological function of miR-1296 in HCC. [score:1]
h An inverse correlation between the levels of miR-1296 and SRPK1 mRNA was observed in HCC tissues. [score:1]
Herein, we discovered that miR-1296 restrained the activation of PI3K/AKT signaling. [score:1]
We next explored the clinical significance of miR-1296 and SRPK1 in HCC patients. [score:1]
These data suggest that combination of miR-1296 and SRPK1 is a potential biomarker for the clinical outcome of HCC patients. [score:1]
These results suggest that miR-1296 and SRPK1 may be promising predictors for the prognosis of HCC patients. [score:1]
Fig. 8PI3K/AKT signaling is essential for the biological function of miR-1296 in HCC. [score:1]
d Hypoxia facilitated the EMT process of Hep3B cells and miR-1296 restoration showed a opposite effect. [score:1]
Moreover, miR-1296 increased resistance to chemotherapeutic treatment and could be used as a new potential biomarker for breast cancer stem cell diagnosis [16]. [score:1]
b The levels of miR-1296 in Hep3B cells cultured in normoxia and hypoxia. [score:1]
4–6 week-old female BALB/c nude mice (Centre of Laboratory Animals, The Medical College of Xi’an Jiaotong University, Xi’an, China) were randomized into two groups (n = 5), and either HCCLM3-miR-1296 or HCCLM3-miR-control cells (1 × 10 [6]); Hep3B-anti-miR-1296 or Hep3B-anti-miR-NC were injected into the tail veins for the establishments of pulmonary metastatic mo del. [score:1]
These results suggest that hypoxia -induced miR-1296 loss promotes the metastasis and EMT of HCC. [score:1]
miR-1296 ameliorates the metastatic potential of HCC cells in mice. [score:1]
We found that miR-1296 was obviously decreased in aggressive HCC tissues compare to non-aggressive tissues (P < 0.05, Fig. 1b). [score:1]
Next, we demonstrated that SRPK1 mediated miR-1296-modulated migration, invasion and EMT process of HCC cells. [score:1]
The hypoxia -induced miR-1296 loss creates a milieu of metastasis facilitation that plays a promoting role in HCC progression. [score:1]
d indicated that modulating AKT phosphorylation reversed the effects of miR-1296 alteration on EMT process of HCC cells. [score:1]
In conclusion, these results indicated that miR-1296 loss functions in hypoxia -induced migration, invasion and EMT events of HCC cells. [score:1]
*Statistically significant Fig. 7The prognostic value of miR-1296 and SRPK1 for HCC patients. [score:1]
Moreover, miR-1296 restoration abolished the promoting effects of hypoxia on migration, invasion and EMT process of HCC cells. [score:1]
Second, the complementary sequences of miR-1296 were identified in the 3’UTR of SRPK1 mRNA. [score:1]
SRPK1 mediates the effects of miR-1296 on HCC cells. [score:1]
Taken together, these data indicate that SRPK1 is a downstream of miR-1296 in HCC. [score:1]
The mutant binding site was generated in the complementary site for the seed region of miR-1296. [score:1]
These data suggest that SRPK1 alteration could mimic miR-1296 -induced metastasis and EMT process in HCC cells. [score:1]
In addition, miR-1296, SRPK1 and their combination were valuable predictors for the prognosis of HCC patients. [score:1]
Notably, an obvious inverse correlation between the levels of miR-1296 and SRPK1 mRNA was revealed by Spearman’s correlation analysis in HCC tissues (P < 0.05, Fig. 4h). [score:1]
Therefore, SRPK1/AKT pathway may be involved in the role of miR-1296 in HCC cells. [score:1]
a Representative HE staining of lung metastases between HCCLM3-miR-1296 cells and control cells. [score:1]
a miR-1296 and its putative binding sequences in the 3′-UTR of SRPK1. [score:1]
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2
[+] score: 219
While in prostate cancer PC3 cells of human beings, the low expression of miR-1296 can upregulate both minichromosome maintenance 2 (MCM2) mRNA and protein, and conversely, its overexpression can lower the level of the both and even shorten the S phase of the cell cycle [6]. [score:8]
On cellular and molecular levels, miR-1296 overexpression plays a evidently suppressive role in the expression of Cyclin D1 and the multiplying of TNBC cell lines [5]. [score:7]
Interestingly, we found that the migration of SNU-216 and NUGC-4 cells was inhibited by miR-1296-5p overexpression, and rescued by constitutively active Rac1-Q61L overexpression (Fig 3B). [score:7]
We also found that the invasion of SNU-216 and NUGC-4 cells was inhibited by miR-1296-5p overexpression, and rescued by constitutively active Rac1-Q61L overexpression (Fig 3C). [score:7]
In this article, our experiment verifies the inhibitive role of miR-1296-5p in the migration and invasion of ERBB2-postive gastric cancer cells that is achieved by suppressing ERBB2 expression and Rac1 activation. [score:7]
Boyden chamber assays showed that the migration and invasion of SNU-216 and NUGC-4 cells were inhibited by miR-1296-5p overexpression or herceptin treatment, and rescued by the overexpression of constitutively active Rac1-Q61L or ERBB2 (Fig 6B and 6C). [score:6]
In ERBB2 -positive gastric cancers, the miR-1296-5p expression is more suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples, suggesting that miR-1296-5p might play a role of tumor metastasis suppressor in ERBB2 -positive gastric cancer. [score:6]
The other studies show that miR-1296 is down-regulated in prostate cancer and triple negative breast cancer (TNBC) samples [5, 6], suggesting that it might have a role as a tumor-suppressor gene in these cancers mentioned above. [score:6]
We have found that miR-1296-5p suppressed the Rac1 activation (Fig 3A) and ERBB2 expression (Fig 4B). [score:5]
We found that miR-1296-5p expression was significantly down-regulated in gastric cancer tissues compared with the non-tumor adjacent normal tissues (Fig 1A). [score:5]
In triple negative breast cancer (TNBC) cell lines and tissues samples, miR-1296 expression was significantly suppressed and increased the sensitiveness of TNBC cells to cisplatin treatment [5]. [score:5]
Less miR-1296-5p -overexpressing cells migrated and invaded onto the bottom surfaces of Boyden chambers significantly than the control miRNA -expressing cells (Fig 2). [score:5]
We further advocate that miR-1296-5p can inhibit cell migration by repressing ERBB2 expression and Rac1 activation in gastric cancer cells. [score:5]
Therefore, miR-1296-5p is a candidate tumor suppressor miRNA molecule in gastric cancer and may be a potential clinical classification marker and therapeutic target for human gastric cancer metastasis. [score:5]
To explore whether ERBB2 was the target gene of miR-1296-5p, we constructed the luciferase reporter vectors with the putative ERBB2 3'-UTR target site for the miR-1296-5p downstream of the luciferase gene (pGL3-ERBB2-3'-UTR). [score:5]
Here, we suggest for the first time that the miR-1296-5p level is inversely correlated with ERBB2 expression in gastric cancers, and miR-1296-5p repressed ERBB2 expression in gastric cancer cells. [score:5]
As expected, the miR-1296-5p expression was suppressed in a majority of ERBB2 -positive gastric cancer samples compared to ERBB2 -negative gastric cancer samples (Fig 5A). [score:4]
Interestingly, in ERBB2 -positive gastric cancers, the miR-1296-5p expression was suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples (Fig 5B). [score:4]
To the best of our knowledge, this is the first study to demonstrate that miR-1296-5p might be involved in regulating the migration and invasion of human gastric cancer cells at least in part via targeting ERBB2/Rac1 signaling pathway. [score:4]
0170298.g003 Fig 3 (A) MiR-1296-5p overexpression inhibited the activation of Rac1, but not Cdc42 and RhoA, in SNU-216 and NUGC-4 gastric cancer cells. [score:4]
These findings illustrated that miR-1296-5p was significantly down-regulated in ERBB2 -positive gastric cancer tissues, especially in ERBB2 -positive metastatic lymph node tissues. [score:4]
This is the first study to demonstrate that miR-1296-5p is down-regulated in lymph node metastatic gastric cancer tissues. [score:4]
0170298.g005 Fig 5. (A) The miR-1296-5p expression is suppressed in a majority of ERBB2 -positive gastric cancer samples (n = 17) when compared to ERBB2 -negative gastric cancer samples (n = 89). [score:4]
The first main observation in the present study is that miR-1296-5p expression is suppressed in a majority of gastric cancer samples when compared to that in normal gastric samples. [score:4]
0170298.g001 Fig 1 (A) The miR-1296-5p expression was suppressed in a majority of gastric cancer samples (n = 106) when compared to normal gastric samples (n = 30). [score:4]
We found that the expression of ERBB2 in miR-1296-5p -transfected cells was extremely depressed than that in control cells (Fig 4B). [score:3]
Therefore, miR-1296-5p was predicted as a tumor-suppressor in gastric cancer progress and metastasis. [score:3]
The 3'-UTR of human ERBB2 containing the putative target site for the miR-1296-5p was chemically synthesized and inserted at the XbaI site, immediately downstream of the luciferase gene in the pGL3-control vector (Promega, Madison, WI) by Integrated Biotech Solutions Co. [score:3]
Taken together, these experiments demonstrated that miR-1296-5p suppressed the Rac1 activation, the migration and invasion of gastric cancer cells. [score:3]
MiR-1296 was found significantly downregulated in prostate cancer tissues, bringing about an obvious decrease in the S phase of the cell cycle [6]. [score:3]
Moreover, the overexpression of miR-1296-5p did not alter the protein level of Rac1 (Supporting information file S1 Fig). [score:3]
Herceptin treatment and miR-1296-5p overexpression had similar capability in retarding gastric cancer cell migration and invasion (Fig 6B and 6C). [score:3]
In view of the fact that ERBB2 was the target gene of miR-1296-5p, we speculated that miR-1296-5p has negative correlation with ERBB2 in gastric cancer tissues. [score:3]
Meanwhile, we also found that miR-1296-5p was significantly down-regulated in lymph node metastatic tissues compared with non-metastatic gastric cancer tissues (Fig 1B). [score:3]
MiR-1296-5p is down-regulated in gastric cancer tissues. [score:3]
MiR-1296-5p is down-regulated in metastatic gastric cancer tissues. [score:3]
ERBB2 as a target gene of miR-1296-5p. [score:3]
Next, we transfected the miR-1296-5p mimic and miRNA mimic control into SNU-216 and NUGC-4 cells and examined the expression of ERBB2. [score:3]
ERBB2 as a target of miR-1296-5p. [score:3]
Taken together, these results showed that ERBB2 was the target gene of the miR-1296-5p. [score:3]
showing the unchanged of Rac1 protein levels in SNU-216 and NUGC-4 cells after miR-1296-5p overexpression. [score:3]
With 106 cases of gastric cancer and 30 cases of non-tumor adjacent normal tissues, we used quantitative real-time PCR to justify whether miR-1296-5p expression was associated with gastric cancer. [score:3]
S1 Fig showing the unchanged of Rac1 protein levels in SNU-216 and NUGC-4 cells after miR-1296-5p overexpression. [score:3]
MiR-1296-5p is down-regulated in ERBB2 -positive gastric cancer tissues. [score:3]
Moreover, miR-1296-5p is obviously down-regulated in ERBB2 -positive gastric cancer samples compared to ERBB2 -negative gastric cancer samples. [score:3]
org) predicted that ERBB2 was the target gene of miR-1296-5p. [score:3]
However, the role of miR-1296-5p as tumor-suppressor in cancer metastasis is still largely unknown. [score:3]
Collectively, these findings cement the fact that miR-1296-5p is a novel regulator of ERBB2 in gastric cancers. [score:2]
MiR-1296-5p suppresses the migration and invasion of gastric cancer cells. [score:2]
MiR-1296-5p suppresses the migration, invasion and Rac1 activation of gastric cancer cells. [score:2]
We found that it was the activation of Rac1, not RhoA and Cdc42, that was significantly inhibited in miR-1296-5p -transfected cells compared to that in control cells (Fig 3A). [score:2]
MiR-1296-5p suppresses Rac1 activation. [score:2]
MiRNA microarray analyses demonstrate that miR-1296 can affect PIM1-STAT3 pathway in PI003 (a novel synthesized small-molecule compound) -induced apoptosis in cervical cancer [7]. [score:1]
In gastric cancer cells, significant decrease of relative luciferase activity was noted when pGL3-ERBB2-3'-UTR was co -transfected with the miR-1296-5p mimic but not with the miRNA mimic control, respectively (Fig 4A). [score:1]
In conclusion, the present study has partially clarified the association between miR-1296-5p and ERBB2 -positive gastric cancer. [score:1]
Human gastric cancer SNU-216 and NUGC-4 cells transiently transfected with miR-1296-5p or control miRNA were agree to migrate (A) and invade (B) in Boyden chambers. [score:1]
72 h after the transfection of miR-1296-5p mimic or miRNA mimic control, the cells were harvested and homogenized with lysis buffer. [score:1]
200 ng pGL3-ERBB2-3'-UTR plus 80 ng pRL-TK (Promega) were transfected in combination with 60 pmol of the miR-1296-5p mimic or miRNA mimic control, respectively. [score:1]
Thus, we examined the activation of RhoA, Rac1 and Cdc42 in miR-1296-5p -transfected cells and the control cells. [score:1]
The ΔCt value was the difference between the Ct value of miR-1296-5p and the Ct value of U6: ΔCt = Ct (miR-1296-5p)—Ct (U6). [score:1]
Not only that, in the apoptosis triggered by PI (a novel synthesized small-molecule compound) in the condition of cervical cancer, miR-1296 could make changes in the PIM1-STAT3 pathway [7]. [score:1]
Luciferase reporter vectors together with the miR-1296-5p mimic or the miRNA mimic control were transfected into SNU-216 and NUGC-4 cells, respectively. [score:1]
For instance, miR-1296 has been proved of its potential linkage with breast cancer chemoresistance and self-renewal capability [4]. [score:1]
0170298.g002 Fig 2 Human gastric cancer SNU-216 and NUGC-4 cells transiently transfected with miR-1296-5p or control miRNA were agree to migrate (A) and invade (B) in Boyden chambers. [score:1]
MiRNA-next generation sequencing analysis reveals the potential association of miR-1296 with breast cancer chemoresistance and self-renewal capability [4]. [score:1]
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3
[+] score: 29
In agreement with these observations, upregulation of miR-1296 decreased the expression of p21 [Cip1], a cyclin -dependent kinase (CDK) inhibitor, and increased the expression of the cell cycle regulator cyclin D1 and Ki67. [score:11]
Moreover, we demonstrated that miR-1296 suppressed FOXO1expression via directly targeting its 3’-UTR. [score:8]
Taken together, our results suggest that upregulation of miR-1296 might play an important role in promoting carcinogenesis and progression of HCC. [score:4]
The key finding of the current study is that miR-1296 is significantly upregulated in HCC cells and tissues, compared with normal hepatocytes and liver tissues. [score:3]
Furthermore, we found that ectopic overexpression of miR-1296 promoted the proliferation, tumorigenicity and cell cycle progression of HCC cells. [score:3]
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4
[+] score: 16
Overexpression of miR-1296 was able to significantly reduce MCM2 expression, indicating that miR -mediated “down-regulation of oncogenes might be a novel therapeutic approach [98]. [score:8]
Mechanistically, GEN dose -dependently induced expression of miR-1296, which is down-regulated in prostate cancer samples. [score:6]
Majid S. Dar A. A. Saini S. Chen Y. Shahryari V. Liu J. Zaman M. S. Hirata H. Yamamura S. Ueno K. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer Cancer Res. [score:2]
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5
[+] score: 14
Other miRNAs from this paper: hsa-mir-21, mmu-mir-21a, mmu-mir-21b, mmu-mir-21c
Obviously, the down-regulation of miR-1296 in A2M* -treated cells may not follow the overall anti-tumour activity of A2M* as this miR is known to up-regulate oncogene MCM2 [30]. [score:7]
The top five down-regulated transcripts belong to LRP12, miR-1296, PREP, LIN9 and NED1 (Fig 7A–7C). [score:4]
As we observed increased expression of PTEN in most tumours, that might override the effect of A2M* at miR-1296. [score:3]
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6
[+] score: 14
The miR-1296-3p is known to play an tumor suppressing and inhibitory role in cancer [120, 121], as well as repress the expression of chromosome maintenance genes that are upregulated in tumors [122]. [score:10]
The most dramatic effect among highly expressed known miRNA was observed for let-7a-3p, as well as: let-7i-5p, miR-1296-3p, miR-340-5p, miR-3184-3p, miR-7-5p, miR-142-5p, and miR-224-3p (Supplementary Table S4). [score:3]
Finally, the miR-1296-3p MiR is intragenic to the JMJD1C gene that has a strong BORIS binding site in its promoter, with a similar situation observed for miR-340-5p (the RNF130 gene), and for miR-224-3p (GABRE gene). [score:1]
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7
[+] score: 13
Other miRNAs from this paper: hsa-mir-370
The same study showed that levels of microRNA (miR)-1296 expression was reduced in carcinoma samples and miR-1296 targeted Mcm2 mRNA probably by binding to the 3′ untranslated region (3′ UTR) of Mcm2. [score:7]
Expression of miR-1296 was enhanced by treatment of PC3 cells with genistein. [score:3]
Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. [score:2]
Treatment with genistein, and TSA, or transfection of miR-1296 to PC3 cells all reduced the percentage of S-phase cells. [score:1]
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8
[+] score: 10
severe (p<0.05) cfa-let-7d, cfa-miR-101, cfa-miR-10a, cfa-miR-1296, cfa-miR-1306, cfa-miR-1307, cfa-miR-130a, cfa-miR-136, cfa-miR-17, cfa-miR-181b, cfa-miR-196b, cfa-miR-197, cfa-miR-215, cfa-miR-22, cfa-miR-30d, cfa-miR-33b, cfa-miR-497, cfa-miR-503, cfa-miR-574, cfa-miR-628, cfa-miR-676 Comparing the miRNA differential expression analyses between disease states obtained by RT-qPCR and RNAseq, we observed discordances between the two methods. [score:5]
severe (p<0.05) cfa-let-7d, cfa-miR-101, cfa-miR-10a, cfa-miR-1296, cfa-miR-1306, cfa-miR-1307, cfa-miR-130a, cfa-miR-136, cfa-miR-17, cfa-miR-181b, cfa-miR-196b, cfa-miR-197, cfa-miR-215, cfa-miR-22, cfa-miR-30d, cfa-miR-33b, cfa-miR-497, cfa-miR-503, cfa-miR-574, cfa-miR-628, cfa-miR-676Comparing the miRNA differential expression analyses between disease states obtained by RT-qPCR and RNAseq, we observed discordances between the two methods. [score:5]
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9
[+] score: 6
With the exception of the patient S2, two groups of miRNAs can be observed, one group in which the expression is lower in the patients with short-OS (miR-211, miR-1207-3p, miR-326, miR-197, let-7b*, miR-1296, miR-4290) and one group that has an opposite expression profile (miR-4321, miR-3610, miR-1914*). [score:5]
As observed from Table S3, the top 10 miRs were the same, except for miR-1200 and miR-766 that replaced miR-197 and miR-1296. [score:1]
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10
[+] score: 4
Locus ID Gene RefSeq Expression Phastcons Status 21019 Intron - AC124066.2 1,12,2,1 0.57 miR-1180 38843 Intron ARL10 - 0,0,3,2 0.99 miR-1271 6150 Intron C10orf33 - 4,0,1,4 1 miR-1287 6746 Intron JMJD1C - 1,4,2,1 1 miR-1296 27738 Intron DNMT3A - 3,12,7,4 0.99 miR-1301 8884 intron FADS1 NM_013402 2,0,9,2 0.34 miR-1908 37600 repeat - - 136,933,146,220 0.03 alt. [score:3]
While writing this paper a new version of miRBase was released, now including six of these miRNAs (mir-1180, mir-1271, mir-1287, mir-1296, mir-1301, and mir-1908). [score:1]
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11
[+] score: 3
24 *** hsa-mir-770-5p 19 *** 75.47 *** hsa-mir-93* 9.5 *** 92.1 - Inhibited differentiation & low cell count *** hsa-let-7b* 4.75 *** 28.64 *** hsa-mir-1224-3p 2.38 *** 51.46 *** hsa-mir-1228 2.38 ** 9.43 *** hsa-mir-1249 1.66 *** 53.17 *** hsa-mir-125a-5p 19 *** 69.8 *** hsa-mir-1260 7.12 *** 61.75 *** hsa-mir-1280 11.88 *** 68.95 *** hsa-mir-129-3p 9.5 *** 65.64 - hsa-mir-1296 9.5 *** 36.36 *** hsa-mir-133a/hsa-mir-133b 42.75 * 0.85 *** hsa-mir-150 4.75 *** 60.37 *** hsa-mir-197 4.75 *** 27.79 *** hsa-mir-204 2.85 *** 27.44 *** hsa-mir-328 0.1 ** 30.87 *** hsa-mir-342-3p 33.25 *** 58. [score:3]
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[+] score: 3
Three target sites were predicted for miR-1296 in the 3′-UTR of both human and pig DDR1, with one out of the three sites altered in one pig variant (i. e. one disrupted poly-miRTS). [score:3]
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13
[+] score: 1
The most significant alignments with human miRNA were obtained with four pre-miRNA (pre-mir-302a, pre-let-7b, pre-mir-1267 and pre-mir-1296; E-value <0.1) and with the two miRNA (mir-365 and mir-31; E-value <0.1) Examples of alignment results show that for some candidates the seed region was perfectly aligned and some others had one or two nucleotide differences (Figure 1). [score:1]
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