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

doi:10.1016/j.apsb.2019.11.009

MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1

Acta Pharm Sin B. 2020 Jun;10(6):1036-1046. doi: 10.1016/j.apsb.2019.11.009. Epub 2019 Nov 16.

Authors

Affiliations

¹ Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
² Department of Prosthodontics, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

Abstract

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.

Keywords: Breast cancer; Chemosensitivity; Drug resistance; HMGB1; MCF-7 cell line; MiR-142-3p.