2. Academic Validation
  3. RBM15 Enhances 5-Fluorouracil Drug Sensitivity and Suppresses Gastric Cancer Progression by Modulating N6-Methyladenosine Modification of ECT2-Dependent IGF2BP3

RBM15 Enhances 5-Fluorouracil Drug Sensitivity and Suppresses Gastric Cancer Progression by Modulating N6-Methyladenosine Modification of ECT2-Dependent IGF2BP3

  • Research (Wash D C). 2026 Feb 2:9:1108. doi: 10.34133/research.1108.
Xingyu Zhu 1 2 3,  Hao Chen 4 5,  Kang Xu 6,  Yuan Liu 1 2,  Han Li 6,  Yaodong Sang 1 2 3,  Yulong Zhao 1 2 3,  Xinyu Liu 1 2 3,  Xiaohan Wang 1 2 3,  Xiaoling Cui 1 2 3,  Baoshan Cai 1 2 3,  Liang Shang 1 2 3,  Changqing Jing 1 2 3,  Wei Chong 1 2 3,  Leping Li 1 2 3
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.
  • 2 Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan 250021, China.
  • 3 Medical Science and Technology Innovation Center, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250021, China.
  • 4 Clinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan 250021, China.
  • 5 Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China.
  • 6 Department of Gastroenterological Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250021, China.
PMID: 41635511 DOI: 10.34133/research.1108
Abstract

Gastric Cancer (GC) remains a leading cause of global Cancer mortality. Analysis of clinical tissues and multiple cohorts (TCGA, ACRG, Singapore, KUGH) associated high RBM15 expression with favorable prognosis. Functional assays in vitro and in vivo demonstrated that RBM15 suppresses GC cell proliferation, migration, and invasion. Integrated RNA-seq and bioinformatics analyses identified the oncogene ECT2 and the epithelial-mesenchymal transition (EMT) pathway as key downstream effectors of RBM15. Mechanistically, RBM15 regulates the m6A methylation of ECT2 mRNA at the 2,909-base pair site, which modulates its binding to the reader protein IGF2BP3, as confirmed by MeRIP, RIP-qPCR, and RNA pull-down assays. A luciferase reporter assay further validated that this m6A modification regulates ECT2 expression. Furthermore, animal and patient-derived Organoid models revealed that RBM15 enhances the sensitivity of GC to 5-fluorouracil (5-FU) chemotherapy in an ECT2-dependent manner. In conclusion, this study defines a novel RBM15/IGF2BP3-ECT2 signaling axis that regulates EMT and chemosensitivity in GC via m6A methylation, providing both mechanistic insights and a potential therapeutic strategy.

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