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

• Published in: Journal of neurochemistry 2025-01, Vol.169 (1), p.e16224
• Main Authors: Wei, Yigong, Zhou, Kun, Wang, Cheng, Du, Xiaolin, Wang, Zhengdi, Chen, Guangtang, Zhang, Huan, Hui, Xuhui
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - immunology; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - physiology; Exosomes - genetics; Exosomes - metabolism; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Humans; Macrophages - immunology; Macrophages - metabolism; Male; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Tumor Escape - genetics
• ISSN: 1471-4159; 1471-4159
• DOI: 10.1111/jnc.16224

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.