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Neoplasma Vol.66, No.2, p.211-221, 2019 |
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Title: MiR-203a functions as a tumor suppressor in bladder cancer by targeting SIX4 | ||
Author: X. Y. Na, X. S. Shang, Y. Zhao, P. P. Ren, X. Q. Hu | ||
Abstract: Increasing evidence indicates that microRNAs (miRNAs) have essential roles in various biological processes, including proliferation, migration, invasion, cell cycle progression and apoptosis. It is considered that miRNA de-regulation contributes to tumor progression and metastasis in various cancers, and MiR-203a has been identified as a tumor suppressor in cancers, such as glioma, gastric cancer and hepatocellular carcinoma. Herein, we established that miR-203a expression is significantly lower in bladder cancer tissues than in adjacent normal tissues, and that low miR-203a expression is associated with poor patient outcome. The over-expression of miR-203a inhibited bladder cancer cell proliferation, invasion, migration and EMT in vitro, and its up-regulation led to bladder cancer cell cycle arrest and apoptosis. This over-expression also inhibited the PI3K/Akt signaling pathway. Bioinformatics prediction software and luciferase reporter assay then confirmed that SIX4 is a direct target of miR-203a. We established negative correlation between SIX4 expression and miR-203a expression in bladder cancer tissues, and SIX4 silencing caused effects similar to miR-203a up-regulation Furthermore, SIX4 over-expression diminished the effects of miR-203a on bladder cancer cells in vitro. In summary, our study determined that miR-203a down-regulation is closely related to tumorigenesis in bladder cancer; thus suggesting that miR-203a is a potential prognostic marker and a potential target in bladder cancer treatment. |
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Keywords: bladder cancer, miR-203a, SIX4, PI3K/Akt, EMT | ||
Published online: 19-Mar-2019 | ||
Year: 2019, Volume: 66, Issue: 2 | Page From: 211, Page To: 221 | |
doi:10.4149/neo_2018_180512N312 |
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