Abstract
Gastric cancer (GC) is primarily associated with Helicobacter pylori (H. pylori) infection, which disrupts gastric mucosa homeostasis, leading to epithelial-mesenchymal transition (EMT) and intestinal metaplasia (IM). We previously found that ELMO1 methylation increased with the progression of chronic gastric inflammation, and its expression was significantly elevated in GC tissues. Further analysis indicated that ELMO1 methylation may interact with Med31. This paper aims to determine the molecular mechanism of ELMO1 methylation in H. pylori-infected GC. The viability, proliferation, and migration of H. pylori-infected AGS cells were detected by cell counting kit-8 (CCK-8), wound healing, and colony information assay, respectively. The methylation status of ELMO1 was determined by methylation-specific PCR (MSP) analysis. mRNA expression levels were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to evaluate protein levels. Co-immunoprecipitation was used to detect proteins interacting with ELMO1. Co-culture experiments were performed to explore the mechanism of ELMO1 methylation in regulating M2 polarization and IM in H. pylori-infected AGS cells. ELMO1 methylation was significantly upregulated in AGS cells upon H. pylori infection. Our data suggest that ELMO1 methylation accelerated H. pylori-induced IM in AGSs by interacting with Med31. Additionally, we found that ELMO1 methylation drives M2 polarization in H. pylori-infected GCs through interaction with Med31. Further study indicated that ELMO1 methylation enhances H. pylori-induced EMT and IM by promoting M2 polarization. This study suggests that ELMO1 methylation interacts with Med31 and activates M2 macrophage polarization s to facilitate EMT and IM in GC with H. pylori infection.
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Relevant experimental data are available from the corresponding author upon reasonable request.
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Funding
This study was supported by the Shenzhen Nanshan District Health and Health System Science and Technology Major Project (No. NSZD2023060).
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Tianyu Lu contributed to the conceptualization, investigation, and writing-original draft. Tingting Yu and Cheng He contributed to the formal analysis, software, and validation. Boyan Huang, Fang Wang, and Liang Zhang contributed to the methodology and data interpretation. Jian Song contributed to the conceptualization, writing- review and editing, and funding acquisition. All authors contributed to the article and approved the final version.
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The study protocol was reviewed and approved by the ethics committee of Southern University of Science and Technology Hospital, approval number (SUSTech-JY202303041).
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Lu, T., Yu, T., He, C. et al. Interaction between ELMO1 DNA methylation and Med31 promotes H. pylori-induced gastric cancer EMT and intestinal metaplasia via M2 polarization. Sci Rep (2026). https://doi.org/10.1038/s41598-026-35314-x
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DOI: https://doi.org/10.1038/s41598-026-35314-x
