Zhao QY, Wei SJ. Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis. World J Gastrointest Oncol 2025; 17(12): 113524 [DOI: 10.4251/wjgo.v17.i12.113524]
Corresponding Author of This Article
Shou-Jiang Wei, MD, Professor, Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, No. 1 Maoyuan Road, Shunqing District, Nanchong 637000, Sichuan Province, China. nsmcwsj@163.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Dec 15, 2025; 17(12): 113524 Published online Dec 15, 2025. doi: 10.4251/wjgo.v17.i12.113524
Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis
Qing-Yun Zhao, Shou-Jiang Wei
Qing-Yun Zhao, Shou-Jiang Wei, Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
Author contributions: Zhao QY performed the experiments, data analysis and wrote the paper; Zhao QY and Wei SJ conceived and designed the study, reviewed and edited the manuscript; all authors read and approved the final manuscript.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: The animal experiments were approved by the Experimental Animal Ethics Committee of North Sichuan Medical College (approval No. 20240520).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Dataset available from the corresponding author at msmcwsj@163.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shou-Jiang Wei, MD, Professor, Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, No. 1 Maoyuan Road, Shunqing District, Nanchong 637000, Sichuan Province, China. nsmcwsj@163.com
Received: August 28, 2025 Revised: September 17, 2025 Accepted: November 6, 2025 Published online: December 15, 2025 Processing time: 106 Days and 1.4 Hours
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 (SLC7A11 and GPX4), 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.
Core Tip: We successfully isolated exosomes from colorectal cancer (CRC) cells. Inhibition of miR-191 in CRC cells suppressed M2 polarization of macrophages. After coculture of macrophages, inhibition of miR-191 induced reactive oxygen species 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 in macrophages. Exosomal miR-191 also accelerated cancer progression in CRC nude mice by promoting M2 polarization of macrophages.
