The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells

作     者：XUHUI ZHAO XIAOMIN HUANG CHUNYAN DANG XIA WANG YUJIAO QI HONGLING LI 

作者机构：The First Clinical Medical CollegeGansu University of Traditional Chinese MedicineLanzhou730000China Department of OncologyGansu People’s HospitalLanzhou730000China The Clinical Medical CollegeNingxia Medical UniversityNingxia750004China 

出 版 物：《Oncology Research》 (肿瘤学研究（英文）)

年 卷 期：2024年第32卷第5期

页      面：999-1009页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Health Commission Key Laboratory of Gastrointestinal Tumour Diagnosis and Treatment 2022 Master/Postdoctoral Fund Project(NHCDP2022005) Gansu Provincial Science and Technology Department Joint Scientific Research Fund Project(23JRRA1545) Gansu Provincial Hospital Intra-Hospital Research Fund Project(22GSYYD-37) International Co-Operation Project of Gansu Provincial Science and Technology Department(No.20YF8WA096). 

主　　题：EBV TGF-β/SMAD4 Glycolysis Gastric cancer 

摘      要：Background:EBV-miR-BARTs exhibit significant relevance in epithelial tumors,particularly in EBVassociated gastric and nasopharyngeal cancers.However,their specific mechanisms in the initiation and progression of gastric cancer remain insufficiently explored.Material and Methods:Initially,EBV-miRNA-BART6-5p and its target gene SMAD4 expression were assessed in EBV-associated gastric cancer tissues and cell lines.Subsequent transfection induced overexpression of EBV-miRNA-BART6-5p in AGS and MKN-45,and downregulation in EBVpositive cells(SUN-719).The subsequent evaluation aimed to observe their impact on gastric cancer cell proliferation,migration,and glycolytic processes,with the TGF-β/SMAD4 signaling pathway value clarified using a TGF-βinhibitor.Results:EBV-miRNA-BART6-5p exhibits pronounced upregulation in EBV-associated gastric cancer tissues and EBV-positive cells,while its target gene SMAD4 demonstrates downregulated expression.Upregulation of it can promote the proliferation and migration of gastric cancer cells.Additionally,We found EBV-miRNA-BART6-5p promotes glycolysis of gastric cancer cells.Inhibition of the TGF-β/SMAD4 signaling pathway resulted in suppressed proliferation and migration of gastric cancer cells,concomitant with a diminished glycolytic capacity.Conclusion:In this study,we found that EBV-miRNA-BART6-5p can target SMAD4,effectively increasing glycolysis in gastric cancer cells by regulating the TGF-β/SMAD4 signaling pathway,thereby enhancing the proliferation and metastasis of gastric cancer cells.Our findings may offer new insights into the metabolic aspects of gastric cancer.