miR-128-3p Reduces Proliferation and Immune Escape in Acute Myeloid Leukemia Through Targeted Regulation of ZEB1

Abstract

microRNAs have received wide attention as potential therapeutic targets. This study explored the action of miR-128-3p in acute myeloid leukemia (AML). miR-128-3p expression in AML was determined by quantitative PCR method. MTT proliferation assay and immunoblot assay were employed to detect proteins related to proliferation and apoptosis in THP-1 cells overexpressing miR-128-3p. RNA immunoprecipitation and dual luciferase reporting system were utilized to verify downstream targets of miR-128-3p. Flow cytometry was conducted to analyze the apoptosis rate and immune escape of THP-1 cells in the T-cell co-culture system. miR-128-3p was lowly expressed in AML patients (reduced by 41.6%). Overexpression of miR-128-3p inhibited THP-1 cell proliferation and immune escape, and stimulated apoptosis. ZEB1 was a downstream target of miR-128-3p, and up-regulation of miR-128-3p inhibited ZEB1 mRNA and protein expression (respectively reduced by 65.8% and 42.0%). Upregulating ZEB1 reversed the inhibitory effect of upregulating miR-128-3p on THP-1 cell proliferation and immune escape. Upregulating ZEB1 promoted PD-L1 protein expression (increased by 0.75-fold). Blocking PD-L1 reversed the promotion of THP-1 cell proliferation and immune escape by upregulating ZEB1. The miR-128-3p/ZEB1/PD-L1 axis is involved in regulating the proliferation and immune escape of AML cells, providing new insights into the molecular mechanism of miR-128-3p in AML and, more importantly, a new target for immunotherapy of AML.

Keywords: Acute myeloid leukemia; PD-1; PD-L1; ZEB1; miR-128-3p.