1.MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1.
Lu LIANG ; Jijun FU ; Siran WANG ; Huiyu CEN ; Lingmin ZHANG ; Safur Rehman MANDUKHAIL ; Lingran DU ; Qianni WU ; Peiquan ZHANG ; Xiyong YU
Acta Pharmaceutica Sinica B 2020;10(6):1036-1046
MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.
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