MiR-133a acts as an anti-oncogene in Hepatocellular carcinoma by inhibiting FOSL2 through TGF-β/Smad3 signaling pathway

MiR-133a 通过 TGF-β/Smad3 信号通路抑制 FOSL2,在肝细胞癌中发挥抗癌基因作用

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作者:Lu Sun, Zhixian Guo, Jihong Sun, Jingjing Li, Zihui Dong, Yize Zhang, Jianan Chen, Quancheng Kan, Zujiang Yu

Abstract

Hepatocellular carcinoma (HCC), one of the most common maligant cancers in the world, is difficult to diagnose in the early time. MicroRNAs (miRNAs), small non-coding RNAs, perform vital functions in cellular differentiation, metabolism and physiological processes. MiR-133a acts as a tumor suppressor in breast, lung and gastric cancer, while the molecular circadian mechanism has not been clear in HCC. In the present study, we certified that the expression of miR-133a decreased in HCC tissues and cell lines and that miR-133a inhibited proliferation, migration and invasion of hepatocellular carcinoma cells. Fos-related antigen 2 (FOSL2), also named FRA-2, was predicted to be a downstream target of miR-133a based on bioinformatic analysis and the prediction was verified by Western Blot, qRT-PCR and luciferase reporter assay. In addition, there was a negative correlation between miR-133a and FOSL2 expression in HCC samples. Furthermore, we verified that overexpression of miR-133a suppressed biological behaviour of HCC through TGF-β/Smad3 signaling pathway. In brief, miR-133a may be a potential prognostic biomarker and may thus be a new therapy in HCC.

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