Inhibiting exosomal miR-191 can induce ferroptosis in macrophages, thereby delaying the progression of colorectal cancer

Abstract

Colorectal cancer (CRC) is a malignant tumor with high incidence and mortality rates. Multiple studies have shown that exosomal miR-191 has an oncogenic role in various cancers. Current evidence suggests that M2 tumor-associated macrophages (TAMs) are key immunosuppressive cells that induce tumor growth, angiogenesis and epithelial mesenchymal transition. Therefore, M2 TAMs are a potential target for immunotherapy. However, whether CRC-derived exosomal miR-191 can affect CRC progression by altering macrophage polarization has not been reported. Previous studies have predominantly focused on exosomal microRNAs that directly regulate tumor cell proliferation, whereas this study reveals the mechanism by which exosomal miR-191 influences macrophage ferroptosis M2 polarization through indirect regulatory pathways. The objective of this study is to explore the association between miR-191, macrophage ferroptosis, and M2-type polarization: (1) Inhibiting miR-191 significantly reduces its expression in colorectal cancer cells and their exosomes, thereby preventing M2 macrophage polarization; (2) Downregulation of miR-191 accelerates ferroptosis to suppress inflammatory responses and M2 polarization of macrophages in colorectal cancer cells; and (3) Exosomes carrying miR-191 from colorectal cancer cells promote disease progression by inducing M2 macrophage polarization.

Keywords: Colorectal cancer; MicroRNA-191; Ferroptosis; Reactive oxygen species; Macrophage; Inflammation

Core Tip: Inhibiting miR-191 effectively suppresses macrophage M2 polarization by inducing the production of reactive oxygen species in colorectal cancer cells, triggering ferroptosis and subsequent apoptosis. Exosomal miR-191 may become a potential therapeutic target with significant implications for achieving precise diagnosis, precise treatment, and early disease prevention.