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.

据报道，MiR-142-3p在乳腺癌中起着抑癌作用。然而，miR-142-3p对乳腺癌细胞耐药性的调控作用及其潜在机制仍然未知。在这里，我们发现miR-142-3p在耐阿霉素（DOX）的MCF-7细胞系（MCF-7 / DOX）中显着下调。MiR-142-3p过表达增加了DOX敏感性并增强了DOX诱导的乳腺癌细胞凋亡。高迁移率族框1（HMGB1）是miR-142-3p在乳腺癌细胞中的直接功能靶标，而miR-142-3p则负调控HMGB1的表达。此外，HMGB1的过表达显着逆转了miR-142-3p上调介导的凋亡促进和自噬抑制。综上所述，miR-142-3p过表达可能通过靶向HMGB1来抑制自噬并提高乳腺癌细胞对DOX的药物敏感性。miR-142-3p / HMGB1轴可能是调节乳腺癌患者耐药性的新靶标。