MicroRNA-133b suppresses bladder cancer malignancy by targeting TAGLN2-mediated cell cycle

作者:Zhao, Feng; Zhou, Liu-Hua; Ge, Yu-Zheng; Ping, Wen-Wen; Wu, Xin; Xu, Zhong-Le; Wang, Min; Sha, Zuo-Liang; Jia, Rui-Peng*
来源:Journal of Cellular Physiology, 2019, 234(4): 4910-4923.
DOI:10.1002/jcp.27288

摘要

MicroRNAs (miRNAs), a group of small noncoding RNAs, are widely involved in the regulation of gene expression via binding to complementary sequences at 3-untranslated regions (3-UTRs) of target messenger RNAs. Recently, downregulation of miR-133b has been detected in various human malignancies. Here, the potential biological role of miR-133b in bladder cancer (BC) was investigated. In this study, we found the expression of miR-133b was markedly downregulated in BC tissues and cell lines (5637 and T24), and was correlated with poor overall survival. Notably, transgelin 2 (TAGLN2) was found to be widely upregulated in BC, and overexpression of TAGLN2 also significantly increased risks of advanced TMN stage. We further identified that upregulation of miR-133b inhibited glucose uptake, invasion, angiogenesis, colony formation and enhances gemcitabine chemosensitivity in BC cell lines by targeting TAGLN2. Additionally, we showed that miR-133b promoted the proliferation of BC cells, at least partially through a TAGLN2-mediated cell cycle pathway. Our results suggest a novel miR-133b/TAGLN2/cell cycle pathway axis controlling BC progression; a molecular mechanism which may offer a potential therapeutic target.