ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1612935
This article is part of the Research TopicEffects of Lactic Acid and Lactylation on Epigenetic Modifications and Gene Expression in TumorView all 4 articles
Novel RNA-methylase HNRNPC promotes gastric cancer tumorigenesis by triggering the lactate-induced ferroptosis resistance
Provisionally accepted
- Zibo Central Hospital, Shandong, China
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Emerging evidence gradually indicates that lactate and iron-induced cell death plays important role in gastric cancer (GC) progression. Here, this study focused on the effect of ferroptosis-related N6-methyladenosine (m6A) modification on GC progression. The elevated Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) expression positively fortified the aerobic glycolysis and lactate accumulation in GC. The exogenous lactate accelerated the proliferation, oxaliplatin resistance and aerobic glycolysis in GC that inhibited by HNRNPC silencing. Moreover, HNRNPC silencing up-regulated the iron concentration accumulation and ferroptosis, and the exogenous lactate and ferrostatin-1 (Fer-1, ferroptosis specific inhibitor) co-administration reduced the iron concentration. Mechanistically, MCT1 was identified as the downstream target of HNRNPC, and HNRNPC targeted MCT1 to fortify the lactate accumulation, thereby accelerating the ferroptosis resistance in GC. Overall, these findings revealed the novel role of ferroptosis-related HNRNPC on GC lactate accumulation and lactate-induced tumorigenesis in GC tumor microenvironment. The data revealed the importance of HNRNPC for lactate metabolism in GC tumor microenvironment, as well as the synergistic effect of HNRNPC on lactate-induced ferroptosis resistance.
Keywords: ferroptosis, hnRNPC, Lactate, mct1, gastric cancer
Received: 16 Apr 2025; Accepted: 19 Aug 2025.
Copyright: © 2025 Yang, Yang, Shen and Cui. 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: Jian Yang, Zibo Central Hospital, Shandong, China
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