Exosomal miR-191 Promotes Colorectal Cancer Progression - Inducing M2 Macrophage Polarization and Inhibiting Ferroptosis

Sep 28, 2026

BACKGROUND: Multiple exosomal microRNAs have been reported to affect colorectal cancer (CRC) cells, but the role and mechanism of exosomal miR-191 in CRC remain unclear. AIM: Explore how miR-191 contributes to CRC. METHODS: CRC cell-derived exosomes were extracted and identified; after macrophage coculture, polarization was assessed by flow cytometry (CD68/CD163), cytokine ELISA (IL-4/IL-10), western blotting, and immunofluorescence, with ROS, ferroptosis-related proteins, and apoptosis measured by flow cytometry, western blotting, and TUNEL. RESULTS: miR-191 inhibition reduced M2 polarization and triggered ROS production, ferroptosis, and apoptosis; silencing exosomal miR-191 weakened CRC development and slowed tumor progression in nude mice. CONCLUSION: Exosomal miR-191 inhibition attenuates CRC progression by inducing macrophage ferroptosis and modulating the tumor microenvironment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Background

Aim

Methods

Results

Conclusion

Key Words

Core Tip

Citation

| W | J | G | O | World Journal of
Gastrointestinal Oncology | | --- | --- | --- | --- | --- | Submit a Manuscript: [https://www.f6publishing.com](https://www.f6publishing.com) World J Gastrointest Oncol 2025 December 15; 17(12): 113524 DOI: 10.4251/wjgo.v17.i12.113524 ISSN 1948-5204 (online) ORIGINAL ARTICLE Basic Study Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis Qing-Yun Zhao, Shou-Jiang Wei Specialty type: Oncology Provenance and peer review: Unsolicited article; Externally peer reviewed. Peer-review model: Single blind Peer-review report’s classification Scientific Quality: Grade A, Grade B, Grade B Novelty: Grade A, Grade B, Grade B Creativity or Innovation: Grade A, Grade A, Grade B Scientific Significance: Grade A, Grade A, Grade A P-Reviewer: Da MX, PhD, China; Huang RR, PhD, Assistant Professor, China; Li AL, Assistant Professor, China Received: August 28, 2025 Revised: September 17, 2025 Accepted: November 6, 2025 Published online: December 15, 2025 Processing time: 106 Days and 0.9 Hours 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 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](nsmcwsj@163.com) 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. WJGO [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 15, 2025 Volume 17 Issue 12 Zhao QY et al. Functions of exosomal miR-191 in CRC 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. Key Words: Colorectal cancer; MiR-191; Exosome; Macrophages; Ferroptosis; M2 polarization ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved. 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 apop

FAQs

What is the main purpose of the study on miR-191 in colorectal cancer?

The study explores the roles of miR-191 in colorectal cancer and clarifies how exosomal miR-191 influences tumor progression through macrophage behavior and ferroptosis.

How were M2 macrophage polarization and related markers evaluated?

After macrophage coculture, polarization was determined by flow cytometry for CD68 and CD163, ELISA for IL-4 and IL-10, western blotting for CHIT3 and arginase-1, and immunofluorescent staining.

What happens to CRC cells when exosomal miR-191 is inhibited?

Inhibiting miR-191 induces ROS production, ferroptosis, and apoptosis in CRC cells and prevents M2 macrophage polarization, thereby weakening CRC development.

Sep 28, 2026

Uploaded by supergirl