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Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis.

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World journal of gastrointestinal oncology 2025 Vol.17(12) p. 113524
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Zhao QY, Wei SJ

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[BACKGROUND] Multiple exosomal microRNAs were reported to have a significant role in colorectal cancer (CRC) cells.

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APA Zhao QY, Wei SJ (2025). Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis.. World journal of gastrointestinal oncology, 17(12), 113524. https://doi.org/10.4251/wjgo.v17.i12.113524
MLA Zhao QY, et al.. "Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis.." World journal of gastrointestinal oncology, vol. 17, no. 12, 2025, pp. 113524.
PMID 41480226

Abstract

[BACKGROUND] Multiple exosomal microRNAs were reported to have a significant role in colorectal cancer (CRC) cells. The function and mechanism of exosomal miR-191 in CRC have not been clearly elucidated.

[AIM] To explore the roles of miR-191 in CRC.

[METHODS] Supernatant exosomes from CRC cells were extracted and identified. After coculture, macrophage polarization was determined using flow cytometry for the markers cluster of differentiation (CD) 68 and CD163, enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-4 and IL-10, western blotting for chitinase-like protein 3 and arginase-1 expression, and immunofluorescent staining for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate. Reactive oxygen species (ROS) level, ferroptosis-related proteins ( and ), and apoptosis were determined with flow cytometry, western blotting, and TUNEL staining. We performed in vivo experiments to determine the function of exosomal miR-191 and M2 macrophage polarization.

[RESULTS] We successfully isolated exosomes from CRC cells. Inhibition of miR-191 in CRC cells suppressed M2 polarization of macrophages. After coculture of macrophages, inhibition of miR-191 induced ROS production, ferroptosis, and apoptosis of CRC cells. Silencing of exosomal miR-191 from CRC cells prevented M2 polarization of macrophages, and weakened CRC development by inducing ferroptosis. Exosomal miR-191 accelerated cancer progression in CRC nude mice by promoting M2 polarization of macrophages.

[CONCLUSION] Inhibition of exosomal miR-191 attenuated CRC progression by inducing ferroptosis in macrophages. This study revealed a novel mechanism by which exosomal miR-191 modulates the tumor microenvironment.

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