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 

机构地区：[1]The First Clinical Medical College,Gansu University of Traditional Chinese Medicine,Lanzhou,730000,China [2]Department of Oncology,Gansu People’s Hospital,Lanzhou,730000,China [3]The Clinical Medical College,Ningxia Medical University,Ningxia,750004,China

出　　处：《Oncology Research》2024年第5期999-1009,共11页肿瘤学研究（英文）

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).

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.

关 键 词：EBV TGF-β/SMAD4 GLYCOLYSIS Gastric cancer 

分 类 号：R73-37[医药卫生—肿瘤]