ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1612041
This article is part of the Research TopicUnraveling circRNAs and miRNAs: Key Regulators in Immune-Related DiseasesView all 7 articles
The Role of ZC3H13 in Promoting M2 Macrophage Infiltration via m6A Methylation in Esophageal Squamous Cell Carcinoma Tumor Progression
Provisionally accepted
- 1Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
- 2Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong Province, China
- 3The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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In this study, we investigated the role of Zinc finger CCCH-type containing 13 (ZC3H13) within the tumor microenvironment of esophageal squamous cell carcinoma (ESCC-TME). ZC3H13 was identified as a key m6A methyltransferase positively associated with m6A methylation in ESCC tissues. Mutations in ZC3H13 disrupted the nuclear translocation of METTL14 and METTL3. Silencing ZC3H13 inhibited ESCC tumor growth and reduced M2 macrophage infiltration, alongside downregulating the expression of CCL5 and CXCL8 mRNA. Moreover, m6A modification enhanced the stability of CXCL8 transcripts. ESCC tumors promoted M0-to-M2 macrophage polarization through the CXCL8–CXCR2 axis, thereby supporting tumor proliferation. Overall, this study underscores the critical link between ZC3H13-mediated m6A modification, chemokine regulation, and immune microenvironment remodeling in ESCC, ultimately facilitating tumor progression.
Keywords: ESCC (Esophageal squamous cell carcinoma), M2 macrophage, M6A, TME(tumor microenvironment), ZC3H13
Received: 15 Apr 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Yan, Xu, Gong, Liang, Yang, Zheng and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuzhen Zheng, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, 510060, Guangdong Province, China
Junye Wang, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, China
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