miR-302b suppresses cell invasion and metastasis by directly targeting AKT2 in human hepatocellular carcinoma cells
- 253 Downloads
MicroRNAs (miRNAs) have been shown to play essential roles in regulating the activity of human hepatocellular carcinoma (HCC) cells, thereby contributing to the suppression of invasion and metastasis. In this study, using gain and loss of function assays, we demonstrated that miR-302b was frequently down-regulated in clinical HCC specimens, as compared with 15 corresponding adjacent normal tissues. Overexpression of miR-302b suppressed HCC cell invasion and metastasis. Regulation of NF-κB and matrix metalloproteinase (MMP)-2 expression by miR-302b was mediated via AKT2 in SMMC-7721 cells. Silencing AKT2 produced effects similar to those of miR-302b overexpression, which included inhibiting SMMC-7721 cell invasion and metastasis and dereasing NF-κB and MMP-2 expression. Furthermore, overexpression of AKT2 attenuated the effects of miR-302b overexpression. Taken together, our findings indicate that miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2, suggesting that miR-302b might represent a potential therapeutic target for HCC intervention.
KeywordsmiR-302b AKT2 Cell invasion Cell metastasis Hepatocellular carcinoma
This work was funded by The National Natural Science Foundation of China (81402008), The Fundamental Research Funds for the Central Universities (08142006), The National Natural Science Foundation of China (31100921), The National Natural Science Foundation of China (5143827), and The Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT: 1171).
- 7.Su J, Wang Q, Liu Y, Zhong M. miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Mol Cell Biochem. 2014.Google Scholar
- 8.Xiang Q, Chen W, Ren M, Wang J, Zhang H, Deng DY, et al. Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET. Clin Cancer Res. 2014; 13–2620.Google Scholar
- 11.Villegas-Comonfort S, Castillo-Sanchez R, Serna-Marquez N, Cortes-Reynosa P, Salazar EP. Arachidonic acid promotes migration and invasion through a PI3K/Akt-dependent pathway in MDA-MB-231 breast cancer cells. Prostaglandins Leukot Essent Fatty Acids. 2014; 01.007Google Scholar