ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmune landscape and therapeutic barriers in gastrointestinal cancersView all 4 articles
TRPM6 acts as a prognostic biomarker and mediates Mg2+ dependent tumor suppression in colon adenocarcinoma
Provisionally accepted
- 1Shenzhen Nucleus Gene Technology Co., Ltd., Shenzhen, China
- 2Northwest University, Xi'an, China
- 3Shaanxi Provincial People's Hospital, Xi'An, China
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Colon adenocarcinoma (COAD) is a malignant neoplasm derived from colonic epithelial cells with poor prognosis in advanced stages. This study aimed to identify critical molecular regulators of COAD and develop robust biomarkers for prognosis and therapy. Transcriptome data from public databases were analyzed: differential expression of TRPM family genes in COAD and pan-cancer pathogenic associations of TRPM6 were assessed via the Wilcoxon test, with analyses of consensus molecular subtypes, clinical relevance, and survival also performed. TRPM6-regulated differentially expressed genes (DEGs) were identified for functional enrichment, and immune/tumor microenvironment correlations were evaluated using the Spearman test. In vitro, HCT116 and SW480 cells were transfected with TRPM6 siRNAs, with proliferation (CCK-8), migration (Transwell), and marker expression (RT-qPCR) assessed. Results showed TRPM family genes, particularly TRPM4 and TRPM6, had differential expression across COAD subtypes/stages, with high expression correlating with favorable prognosis. TRPM6 regulates cancers via neural pathways, associates with immune/tumor microenvironments, and has pan-cancer diagnostic value. TRPM6 knockdown promoted colon cancer cell proliferation and migration, while concurrent TRPM6 knockdown and high Mg2+ treatment attenuated Mg2+-mediated tumor suppression. These findings highlight TRPM6 as a pivotal mediator of Mg2+ functions and a valuable candidate for COAD prognostic classification and therapeutic intervention, providing a foundation for future studies on its regulatory roles in tumor progression and Mg2+-based therapies.
Keywords: Colon adenocarcinoma, transient receptor potential melastatin channel family genes, Magnesium, Pan-cancer, prognosis
Received: 15 Aug 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Cao, Ren, Yu, Wang, Zhang and Chen. 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:
Hezi Zhang
Erfei Chen
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