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Updated: May 31, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
RBM15 transcription activated by EGR1 stimulates gastric cancer proliferation and metastasis by enhancing m6A
Lu Yang1, Yongsheng Chang1, Wenjing Li1
1Department of Gastroenterology, The First Affiliated Hospital of Henan University of Medicine, 88 Jiankang Road Weihui, Xinxiang, Henan, 453100, China.
Abstract:
Gastric cancer is one of the most common malignant tumors worldwide, and its morbidity and mortality are among the highest among malignant tumors. RNA binding motif protein 15 (RBM15) has been confirmed to be a proto-oncogene in a variety of tumors, and it is also highly expressed in gastric cancer. However, its specific mechanism of role in gastric cancer progression remains unclear. The relationship between RBM15, ras responsive element binding protein 1 (RREB1), and transcription factor early growth responsive gene-1 (EGR1) was predicted by bioinformatics analysis. Meanwhile, the proliferation, stemness, angiogenesis, invasion, and migration of gastric cancer cells were detected by MTT, sphere formation, tube formation, Transwell, and scratch assays. The N6-methyladenosine (m6A) methylation level of RREB1 was determined by MeRIP assay. The stability of RREB1 mRNA was assessed via Actinomycin D. Binding of RBM15 or insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to RREB1, and EGR1 to RBM15 was confirmed by RIP and ChIP assay, respectively. A xenograft tumor model was constructed to analyze the effect of RBM15/RREB1 axis on tumor growth in vivo. RBM15 was highly expressed in gastric cancer. Knockdown of RBM15 inhibited the proliferation, stemness, angiogenesis, invasion, and migration of gastric cancer cells. RBM15 enhanced the stability of RREB1 mRNA by driving the m6A modification of RREB1 through recruiting IGF2BP2. EGR1 stimulated the activation of RBM15 transcription, thereby affecting RREB1's expression. The RBM15/RREB1 axis promotes gastric cancer tumor growth in vivo. This study confirmed that EGR1 activated RBM15 transcription, which mediated the m6A modification of RREB1 mRNA by recruiting IGF2BP2, thereby promoting malignant progression in gastric cancer. The discovery of this pathway provides a new perspective for revealing the pathogenesis of gastric cancer.
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