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

Lipeng Jiang; Chunyan He; Xin Zhang; Yan Chen; Guang Li

doi:10.21037/tcr.2020.02.14

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

Transl Cancer Res. 2020 Mar;9(3):1851-1860. doi: 10.21037/tcr.2020.02.14.

Authors

Lipeng Jiang^{1

2}, Chunyan He³, Xin Zhang², Yan Chen⁴, Guang Li¹

Affiliations

¹ Department of Radiotherapy, The First Hospital of China Medical University, Shenyang 110001, China.
² Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
³ Department of Prosthodontics, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
⁴ Department of Radiotherapy, Affiliated Hospital of Chifeng University, Chifeng 024000, China.

Abstract

Background: MicroRNAs (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.

Methods: In 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.

Results: Our 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.

Conclusions: Taken 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.

Keywords: apoptosis; miR-193b-5p; proliferation; radio-sensitivity; tongue cancer.