MiR-758-3p suppresses proliferation, migration and invasion of hepatocellular carcinoma cells via targeting MDM2 and mTOR

• Published in: Biomedicine & pharmacotherapy 2017-12, Vol.96, p.535-544
• Main Authors: Jiang, Dan, Cho, William C., Li, Zhenhao, Xu, Xiangrong, Qu, Yuliang, Jiang, Zhongjia, Guo, Le, Xu, Guangxian
• Format: Article
• Language: English
• Subjects: Adult; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Movement - physiology; Cell Proliferation - physiology; Female; HEK293 Cells; Hep G2 Cells; Hepatocellular carcinoma(HCC); Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mechanistic target of rapamycin(mTOR); MicroRNAs - biosynthesis; Middle Aged; MiR-758-3p; Mouse double minute 2 homolog (MDM2); Neoplasm Invasiveness - pathology; Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors; Proto-Oncogene Proteins c-mdm2 - metabolism; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.10.004

•MiR-758-3p is down-expressed in HCC.•MiR-758-3p suppresses HCC cells proliferation, migration and invasion.•MiR-758-3p can target MDM2 and mTOR directly and inhibit their expression.•Down-regulation of MDM2 and mTOR can inhibit HCC cells proliferation, migration and invasion.•MDM2-p53 cycle and mTOR pathways are involved in the mechanism miR-758-3p effects HCC. Hepatocelluar carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide and among the leading causes of cancer-related death. Although deregulation of microRNAs has been frequently described in HCC, imperfection is known about the precise molecular mechanisms by which microRNAs modulate the process of tumorogenesis and behavior of cancer cells. In this study, we demonstrated that miR-758-3p could suppress cell proliferation, migration and invasion in hepatocellular carcinoma cells. We screened and identified two novel miR-758-3p targets, MDM2 and mTOR. Up-regulation of miR-758-3p could specifically and markedly down-regulate the expression of MDM2 and mTOR. Additionally, miR-758-3p over-expression displayed significant suppression in HCC development. To identify the mechanisms, we further investigated the P53 and mTOR pathway and found that p-p70S6 kinase(Ser371), p-p70 S6 kinase(Thr389) and p-4E-BP1were dramatically down-regulated after miR-758-3p transfection, while an enhanced expression of P53, AKT and PRAS40 were visualized, thus suggesting that the role of miR-758-3p in HCC progression may be associated with MDM2-p53 and mTOR signaling pathways. Collectively, our results indicate that miR-758-3pserves as a tumor suppressor and plays a crucial role in inhibiting the proliferation, migration and invasion of HCC via targeting MDM2 and mTOR and implicate its potential application in cancer therapy.