El-Arabey AA. Letter to the Editor: Exosomal miR-191 activates the NF-κB pathway to drive M2 macrophages polarization in colorectal cancer. World J Gastrointest Oncol 2026; 18(6): 117110 [DOI: 10.4251/wjgo.v18.i6.117110]
Corresponding Author of This Article
Amr Ahmed El-Arabey, PhD, Assistant Professor, Department of Health Specialties, Basic Sciences and their Applications, Applied College, King Khalid University, Abha 61413, Asir, Saudi Arabia. ph.amrcapa@gmail.com
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Immunology
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letter
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El-Arabey AA. Letter to the Editor: Exosomal miR-191 activates the NF-κB pathway to drive M2 macrophages polarization in colorectal cancer. World J Gastrointest Oncol 2026; 18(6): 117110 [DOI: 10.4251/wjgo.v18.i6.117110]
World J Gastrointest Oncol. Jun 15, 2026; 18(6): 117110 Published online Jun 15, 2026. doi: 10.4251/wjgo.v18.i6.117110
Letter to the Editor: Exosomal miR-191 activates the NF-κB pathway to drive M2 macrophages polarization in colorectal cancer
Amr Ahmed El-Arabey
Amr Ahmed El-Arabey, Health and Medical Research Center, King Khalid University, Abha 61413, Asir, Saudi Arabia
Amr Ahmed El-Arabey, Center of Bee Research and its Products, King Khalid University, Abha 61413, Asir, Saudi Arabia
Amr Ahmed El-Arabey, Department of Health Specialties, Basic Sciences and their Applications, Applied College, King Khalid University, Abha 61413, Asir, Saudi Arabia
Author contributions: El-Arabey AA solely conceived and designed the study, performed data acquisition, analysis, and interpretation, drafted and critically revised the manuscript, approved the final version for publication, and takes full responsibility for the accuracy and integrity of the work.
Supported by Deanship of Research and Graduate Studies at King Khalid University - Small Research Project, No. RGP.1/260/46.
Conflict-of-interest statement: The author declares no conflict of interest.
Corresponding author: Amr Ahmed El-Arabey, PhD, Assistant Professor, Department of Health Specialties, Basic Sciences and their Applications, Applied College, King Khalid University, Abha 61413, Asir, Saudi Arabia. ph.amrcapa@gmail.com
Received: November 28, 2025 Revised: December 20, 2025 Accepted: January 6, 2026 Published online: June 15, 2026 Processing time: 193 Days and 12 Hours
Abstract
I read with great interest the recent article entitled "Exosomal miR-191 promotes colorectal cancer progression by inducing M2 macrophage polarization and inhibiting ferroptosis" by Zhao and Wei published in the World Journal of Gastrointestinal Oncology. In colorectal cancer (CRC), exosomes play an important role in intercellular communication by delivering carcinogenic substances including microRNAs, which modify the tumor microenvironment to promote immune evasion, angiogenesis, and metastasis. It is widely recognized that miR-191 activates the NF-κB signaling pathway, which plays a significant role in the responses of cancer and inflammation to inflammatory and immunological stimuli. In this study, I elucidate the molecular pathway through which exosomal miR-191, originating from CRC cells, facilitates M2 macrophage polarization via NF-κB activation, consequently accelerating tumor growth. Bioinformatic study of The Cancer Genomic Atlas datasets found a significant positive correlation between NF-κB pathway activity and M2 macrophage infiltration in CRC tissues. These findings highlight the miR-191/NF-κB/M2 macrophage axis as a key mediator for macrophages polarization as well as tumor immune regulation and a potential therapeutic target in CRC patients.
Core Tip: Exosomal miR-191 is becoming a crucial pathway of how inflammatory signaling works within tumor microenvironment of colorectal cancer. By activating NF-κB, miR-191 can change the tumor microenvironment to make it immunosuppressive and pro-angiogenic, via shifting the polarization into M2 macrophages. Utilizing The Cancer Genomic Atlas data analyzed via tumor immune estimation resource, version 3, NF-κB1 expression correlated positively with M2 macrophage infiltration, whereas NF-κB1 -mutant tumors had lower macrophage infiltration. Elevated M2 infiltration predicted a shorter disease-free duration in the NF-κB1-high sample, indicating a context-dependent prognostic factor and highlighting the miR-191/NF-κB/M2 macrophages axis as a therapeutic target.
