MiR-193b-5p inhibits proliferation and enhances radio-sensitivity by downregulating the AKT/mTOR signaling pathway in tongue cancer.

Abstract

BackgroundMicroRNAs (miRNAs) have been found to have functions regulating cell proliferation, differentiation and apoptosis, thereby regulating the occurrence, development and prognosis of tumors. MiR-193b-3p is well-known for its tumorigenic effect, but there are few studies on miR-193b-5p, and its role in tongue cancer has not been reported.MethodsIn the present research, we investigated the specific role of miR-193b-5p in tongue cancer. MiR-193b-5p mimics were transfected into tongue cancer cell lines CAL27 and TCA-8113 to generate miR-193b-5p overexpression cells. CCK-8, clonogenic assay, wound healing assay, transwell and flow cytometry analysis were performed to detect cell proliferation, migration, invasion and apoptosis.ResultsOur data showed that the exogenous overexpression of miR-193b-5p blocked the proliferation, inhibited the phosphorylation of AKT and mTOR, and downregulated the levels of Cyclin D1 and P70 of CAL27 and TCA-8113 cells. We predicted that miR-193b-5p suppressed the proliferation of cancer cells by inhibiting the AKT/mTOR pathway. MiR-193b-5p mimics also induced the apoptosis of CAL27 and TCA-8113 cells by inhibiting the expression of Bcl2 and promoting the levels of Active-Caspase3 and Bax. Furthermore, a marked decline in the migration and invasiveness of tongue cancer cells transected with miR-193b-5p mimics was observed. According to the results of western blot, miR-193b-5p downregulated the levels of the epithelial-to-mesenchymal transition (EMT) markers, including N-cad, Vimentin, Snail and Slug, while upregulating E-cad expression level in CAL27 and TCA-8113 cells, suggesting that miR-193b-5p inhibited the migration and invasion by reversing the EMT process. In addition, miR-193b-5p mimics inhibited the formation of clonogenic colonies of CAL27 and TCA-8113 cells after irradiation.ConclusionsTaken together, miR-193b-5p mimics block cell proliferation, migration and invasion and induce apoptosis by inhibiting the AKT/mTOR signaling pathway; they also reversed EMT progression and inhibited the radio-resistance of tongue cancer cells. Our results provide a potential target for the clinical treatment of human tongue cancer.