MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

Abstract

It has been reported that persistent or excessive autophagy promotes cancer cell death during chemotherapy, either by enhancing the induction of apoptosis or mediating autophagic cell death. Here, we show that miR-15a and miR-16 are potent inducers of autophagy. Rictor, a component of mTORC2 complex, is directly targeted by miR-15a/16. Overexpression of miR-15a/16 or depletion of endogenous Rictor attenuates the phosphorylation of mTORC1 and p70S6K, inhibits cell proliferation and G1/S cell cycle transition in human cervical carcinoma HeLa cells. Moreover, miR-15a/16 dramatically enhances anticancer drug camptothecin (CPT)-induced autophagy and apoptotic cell death in HeLa cells. Collectively, these data demonstrate that miR-15a/16 induced autophagy contribute partly to their inhibition of cell proliferation and enhanced chemotherapeutic efficacy of CPT.

Keywords:

• autophagy
• Camptothecin
• cell proliferation
• microRNA
• mTOR
• Rictor

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (No. 31371315). The International Cooperation Grant of Shenzhen (GJHZ20140416153718941) and the Shenzhen Peacock Program (KQC201109050084A). The China Postdoctoral Science Foundation Funded Project (No. 2014T70070)