Trichostatin A augments cell migration and epithelial-mesenchymal transition in esophageal squamous cell carcinoma through BRD4/c- Myc endoplasmic reticulum-stress pathway  

作　　者：Yan-Min Chen Wen-Qian Yang Ying-Ying Fan Zhi Chen Yu-Zhen Liu Bao-Sheng Zhao 

机构地区：[1]Department of Thoracic Surgery,The First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China [2]Department of Oncology,The First Affiliated Hospital of Henan Polytechnic University,Jiaozuo 454000,Henan Province,China [3]Henan Medical Science Key Laboratory of Esophageal Cancer Metastasis Translational Medicine,Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China [4]Life Science Research Center,The First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China [5]Department of Gastroenterology,The First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China [6]Department of Anesthesiology,The First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China

出　　处：《World Journal of Gastroenterology》2025年第11期164-182,共19页世界胃肠病学杂志(英文)

基　　金：Supported by the Henan Province Science and Technology Development Plan,No.242102311124;Key Medical Scientific and Technological Project of Henan Province,No.SBGJ202102188;Henan Provincial Medical Science and Technology Project,No.LHGJ20221012;Fundamental Research Funds for the Universities of Henan Province,No.NSFRF240308.

摘　　要：BACKGROUND The causes of death in patients with advanced esophageal cancer are multi-factorial,with tumor metastasis being one of the important factors.Histone acetylation promotes the migration of esophageal squamous cell carcinoma(ESCC)cells,while the histone deacetylase inhibitor(HDACi)shows complex effects on tumor functions.AIM To comprehensively elucidate the impact and molecular mechanisms of trichostatin A(TSA),an HDACi,on cell migration in ESCC through bromodomain-containing protein(BRD4)/cellular myelocytomatosis oncogene(c-Myc)/endoplasmic reticulum(ER)-stress.METHODS The effects of TSA on ESCC cell lines Eca109 and EC9706 migration were evaluated using Transwell assays,with small interfering transfection and pathway-specific inhibitors to elucidate underlying mechanisms.The mRNA levels involved were examined by quantitative real-time polymerase chain reaction.Protein levels of acetylated histones H3(acH3)and acetylated histones H4,BRD4,c-Myc,as well as markers of ER stress and epithelial-mesenchymal transition(EMT),were analyzed using western blot.Additionally,this method was also used to examine acH3 levels in esophageal cancer tissues and adjacent tissues.Patient outcomes were subsequently tracked to identify prognostic indicators using Log-Rank tests and Cox multivariate analysis.RESULTS TSA promoted the migration of ESCC cells by stimulating the EMT process.TSA-mediated histone acetylation facilitated the recruitment of BRD4,a bromodomain-containing protein,triggering the expression of c-Myc.This cascade induced ER stress and enhanced EMT in ESCC cells.To further elucidate the underlying mechanism,we employed various interventions including the ER stress inhibitor 4-phenylbutyric acid,knockdown of c-Myc and BRD4 expression,and utilization of the BRD4 inhibitor carboxylic acid as well as the inhibitor of TSA 1.Mechanist-ically,these studies revealed that TSA-mediated histone acetylation facilitated the recruitment of BRD4,which in turn triggered the expression of c-Myc.This sequential activation in

关 键 词：Esophageal squamous cell carcinoma Histone deacetylase inhibitor Trichostatin A Endoplasmic reticulum stress Epithelial-mesenchymal transition Cell migration 

分 类 号：R73[医药卫生—肿瘤]