Dataset Information

Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells.

ABSTRACT: Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional regulation of GAS41. Here we identified GAS41 as a novel target for endogenous miR-203 and demonstrate an inverse correlation of miR-203 expression with GAS41 in glioma cell lines (HNGC2 and U87). Over expression of miR-203 negatively regulates GAS41 expression in U87 and HNGC2 cell lines. Moreover, miR-203 restrained miR-10b action by suppressing GAS41. GAS41 is essential for repressing p53 in tumor suppressor pathway during cell proliferation. Enforced expression of GAS41 produced contradictory effect on miR-203 but was able to enhance p53 tumor suppressor pathway associated protein. It was also found that miR-203 maintains the stability of p53 as knock down of p53 expression using siRNA resulted in down regulation of pri-miR and mature miR-203 expression. Conversely reconstitution of miR-203 expression induced apoptosis and inhibited migratory property of glioma cells. Taken together, we show that miR-203 is a key negative regulator of GAS41 and acts as tumor suppressor microRNA in glioma.

SUBMITTER: Pal D

PROVIDER: S-EPMC4965126 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells.

Pal Dhananjaya D Mukhopadhyay Debasmita D Ramaiah M Janaki MJ Sarma Pranjal P Bhadra Utpal U Bhadra Manika Pal MP

PloS one 20160728 7

Glioma amplified sequence 41(GAS41) is a potent transcription factor that play a crucial role in cell proliferation and survival. In glioblastoma, the expression of GAS41 at both transcriptional and post transcriptional level needs to be tightly maintained in response to cellular signals. Micro RNAs (miRNA) are small non coding RNA that act as important regulators for modulating the expression of various target genes. Studies have shown that several miRNAs play role in the post-transcriptional r ...[more]

PMID: 27467502

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Project description:MicroRNAs (miRNAs/miRs) are known to play a key role in tumorigenesis and usually serve as therapeutic targets in cancer treatment. In the present study, the inhibitory effects and the targeting miRNAs of withaferin A (WA) were investigated in human lung cancer cells. Different lung cancer cell lines were administrated with different concentrations of WA for different time interval followed by western blot or reverse transcription-quantitative PCR analyses to determine the underlying signaling pathway. The results demonstrated that WA decreased the viability of lung cancer cells in a caspase-dependent manner. Further investigations indicated that treatment with WA induced the expression of proapoptotic molecules, p53 and Bax, and decreased Bcl-2 expression in A549 cells. Notably, the results demonstrated that WA also decreased the motility of lung cancer cells in a dose-dependent manner, at a relatively lower concentration. Western blot analysis revealed increased E-cadherin and decreased vimentin expression levels in lung cancer cells treated with WA. In addition, two oncomiRs, including miR-10b and miR-27a, which regulate the expression of E-cadherin and Bax, respectively, were downregulated in the presence of WA. The ectopic expression of miR-10b mimics was able to recover the WA-decreased motility of lung cancer cells, which was accompanied by a reduction in E-cadherin expression. Conversely, the ectopic expression of miR-27a mimics decreased the expression of Bax and recovered the viability of lung cancer cells attenuated by WA. In addition, the ectopic expression of p53-wild type decreased the expression levels of both miR-10b and miR-27a, whereas p53 knockdown induced their expression. Transient knockdown of p53 decreased the inhibitory effects of WA in the motility and viability of lung cancer cells, suggesting an association between WA-p53-miR-10b/27a and motility/viability. Further investigations demonstrated that p53 knockdown in lung cancer stable cell lines exhibited higher levels of both miR-10b and miR-27a, and higher motility and viability following treatment with WA. However, suppression of miR-10b and miR-27a effectively decreased motility and viability, respectively, following treatment with WA. Taken together, the results of the present study suggest that WA inhibits the functionality of lung cancer cells by decreasing the expression levels of both miR-10b and miR-27a in a p53-dependent manner.

Dataset Information

Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells.

Publications

Regulation of Cell Proliferation and Migration by miR-203 via GAS41/miR-10b Axis in Human Glioblastoma Cells.

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