Exosomal miR‐142‐3p from M1‐polarized macrophages suppresses cell growth and immune escape in glioblastoma through regulating HMGB1‐mediated PD‐1/PD‐L1 checkpoint

Abstract

Glioblastoma (GBM) is one of the most prevalent cancerous brain tumors. Former studies have reported that exosomes derived from M1‐polarized macrophages (M1 exosomes) inhibit tumor occurrence and development through delivery of tumor suppressor genes. Also, microRNA‐142‐3p (miR‐142‐3p) has been verified to function as a tumor suppressor. GBM cell proliferation was evaluated by Cell Counting Kit‐8 (CCK‐8), colony formation assay and 5‐ethynyl‐2′‐deoxyuridine (EdU) assay; cell apoptosis was determined by flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mechanism investigations were conducted for analyzing the molecular mechanism by which miR‐142‐3p and M1 exosomes affect GBM progression. Upregulation of miR‐142‐3p expression was detected in M1‐polarized macrophages and M1 exosomes. M1 exosomes inhibit GBM cell proliferation and trigger cell apoptosis. Functionally, miR‐142‐3p silencing promotes the proliferation and inhibits the apoptosis of GBM cells treated with M1 exosomes. As for molecular mechanism, miR‐142‐3p inhibits GBM cell growth via targeting high‐mobility group box 1 (HMGB1). In addition, miR‐142‐3p/HMGB1 axis affects GBM cell immune escape through modulation of programmed death‐1/programmed death ligand‐1 (PD‐1/PD‐L1) checkpoint. Our study demonstrated that exosomal miR‐142‐3p from M1‐polarized macrophages suppresses cell growth and immune escape in GBM through regulating HMGB1‐mediated PD‐1/PD‐L1 checkpoint.image