Letter to the Editor
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2024; 30(41): 4503-4508
Published online Nov 7, 2024. doi: 10.3748/wjg.v30.i41.4503
MicroRNA-206 as a promising epigenetic approach to modulate tumor-associated macrophages in hepatocellular carcinoma
Davide Ramoni, Fabrizio Montecucco
Davide Ramoni, Fabrizio Montecucco, Department of Internal Medicine, University of Genoa, Genoa 16132, Italy
Fabrizio Montecucco, First Clinic of Internal Medicine, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa 16132, Italy
Author contributions: Montecucco F drafted the manuscript; Ramoni D wrote the full manuscript; All authors have read and approve the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Fabrizio Montecucco, MD, PhD, Full Professor, First Clinic of Internal Medicine, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, Genoa 16132, Italy. fabrizio.montecucco@unige.it
Received: August 9, 2024
Revised: September 27, 2024
Accepted: October 8, 2024
Published online: November 7, 2024
Processing time: 74 Days and 5.9 Hours
Abstract

This letter comments on the recently published manuscript by Huang et al in the World Journal of Gastroenterology, which focused on the immunomodulatory effect of Calculus bovis on hepatocellular carcinoma (HCC) tumor microenvironments (TME) by inhibiting M2-tumor-associated macrophage (M2-TAM) polarization via Wnt/β-catenin pathway modulation. Recent research highlights the crucial role of TAMs and their polarization towards the M2 phenotype in promoting HCC progression. Epigenetic regulation, particularly through microRNAs (miR), has emerged as a key factor in modulating immune responses and TAM polarization in the TME, influencing treatment responses and tumor progression. This editorial focuses on miR-206, which has been found to inhibit HCC cell proliferation and migration and promote apoptosis. Moreover, miR-206 enhances anti-tumor immune responses by promoting M1-polarization of Kupffer cells, facilitating CD8+ T cell recruitment and suppressing liver cancer stem cell expansion. However, challenges remain in understanding the precise mechanisms regulating miR-206 and its potential as a therapeutic agent. Targeting epigenetic mechanisms and improving strategies, whether through pharmacological or genetic approaches, offer promising avenues to sensitize tumor cells to chemotherapy. Understanding the intricate interactions between cancer and non-coding RNA regulation opens new avenues for developing targeted therapies, potentially improving HCC prognosis.

Keywords: Epigenetic regulation; Hepatocellular carcinoma; Non-coding RNAs; MicroRNA-206; Tumor-associated macrophages; Tumor microenvironment

Core Tip: Hepatocellular carcinoma is a highly aggressive tumor often associated with chronic liver disease and cirrhosis with limited treatment options for patients ineligible for surgery or transplantation. Thus, there is an urgent need to explore alternative therapeutic options. This letter highlights the modulation of M2-tumor-associated macrophage polarization via Wnt/β-catenin and other pathways, as well as the role of microRNA (miR)-206 in promoting anti-tumor immunity. miR-206 stimulates M1 Kupffer cell polarization, recruits CD8+ T cells, and inhibits the expansion of liver cancer stem cells. Understanding these mechanisms could pave the way for targeted therapies that improve outcomes for patients with hepatocellular carcinoma.