Original articles
Lu Liang, Jijun Fu, Siran Wang, Huiyu Cen, Lingmin Zhang, Safur Rehman Mandukhail, Lingran Du, Qianni Wu, Peiquan Zhang, Xiyong Yu. MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 1036-1046

MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1
Lu Lianga, Jijun Fua, Siran Wangb, Huiyu Cena, Lingmin Zhanga, Safur Rehman Mandukhaila, Lingran Dua, Qianni Wua, Peiquan Zhanga, Xiyong Yua
a 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;
b 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 DOXinduced 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.
Key words:    Breast cancer    MCF-7 cell line    HMGB1    MiR-142-3p    Drug resistance    Chemosensitivity   
Received: 2019-07-24     Revised: 2019-09-03
DOI: 10.1016/j.apsb.2019.11.009
Funds: The authors gratefully acknowledge the financial support by National Natural Science Foundation of China (Nos. 81330007 and U1601227), the Science and Technology Programs of Guangdong Province (Nos. 2014A050503047 and 2015B020225006, China), National Natural Science Foundation of China (81700382).
Corresponding author: Peiquan Zhang, Xiyong Yu     Email:pqzhang@gzhmu.edu.cn;yuxycn@aliyun.com
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Lu Liang
Jijun Fu
Siran Wang
Huiyu Cen
Lingmin Zhang
Safur Rehman Mandukhail
Lingran Du
Qianni Wu
Peiquan Zhang
Xiyong Yu

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