Upregulation of miR-142-3p Improves Drug Sensitivity of Acute Myelogenous Leukemia through Reducing P-Glycoprotein and Repressing Autophagy by Targeting HMGB1.

miR-142-3p was reported to be downregulated in acute myelogenous leukemia (AML) and acted as a novel diagnostic marker. However, the regulatory effect of miR-142-3p on drug resistance of AML cells and its underlying mechanism have not been elucidated. Here, we found that miR-142-3p was significantly downregulated and high mobility group box 1 (HMGB1) was dramatically upregulated in AML samples and cells, as well as drug-resistant AML cells. P-gp level and autophagy were markedly enhanced in HL-60/ADR and HL-60/ATRA cells. miR-142-3p overexpression improved drug sensitivity of AML cells by inhibiting cell viability and promoting apoptosis, and inhibited P-gp level and autophagy in drug-resistant AML cells, whereas HMGB1 overexpression obviously reversed these effect. HMGB1 was demonstrated to be a target of miR-142-3p, and miR-142-3p negatively regulated HMGB1 expression. In conclusion, our study elucidated that upregulation of miR-142-3p improves drug sensitivity of AML through reducing P-glycoprotein and repressing autophagy by targeting HMGB1, contributing to better understanding the molecular mechanism of drug resistance in AML.