Expression of the methylcytosine dioxygenase ten-eleven translocation-2 and connexin 43 in inflammatory bowel disease and colorectal cancer  

作　　者：Mohammad El-Harakeh Jessica Saliba Kawthar Sharaf Aldeen May Haidar Layal El Hajjar Mireille Kallassy Awad Jana G Hashash Margret Shirinian Marwan El-Sabban 

机构地区：[1]Department of Anatomy,Cell Biology and Physiological Sciences,Faculty of Medicine,American University of Beirut,Beirut 1107,Lebanon [2]UR GPF Laboratory of Biodiversity and Functional Genomics,Faculty of Science,UniversitéSaint-Joseph de Beyrouth,Beirut 1107,Lebanon [3]Department of Biology,Faculty of Sciences,Lebanese University,Beirut 1533,Lebanon [4]Department of Public Health,Faculty of Health Sciences,University of Balamand,Dekwaneh,Sin el Fil 1552,Lebanon [5]Department of Internal Medicine,Division of Gastroenterology and Hepatology,Faculty of Medicine,American University of Beirut,Beirut 1107,Lebanon [6]Department of Experimental Pathology,Immunology and Microbiology,Faculty of Medicine,American University of Beirut,Beirut 1107,Lebanon

出　　处：《World Journal of Gastroenterology》2022年第40期5845-5864,共20页世界胃肠病学杂志（英文版）

摘　　要：BACKGROUND Inflammatory bowel disease(IBD)constitutes a substantial risk factor for colorectal cancer.Connexin 43(Cx43)is a protein that forms gap junction(GJ)complexes involved in intercellular communication,and its expression is altered under pathological conditions,such as IBD and cancer.Recent studies have implicated epigenetic processes modulating DNA methylation in the pathogenesis of diverse inflammatory and malignant diseases.The ten-eleven translocation-2(TET-2)enzyme catalyzes the demethylation,hence,regulating the activity of various cancer-promoting and tumor-suppressor genes.AIM To investigate Cx43 and TET-2 expression levels and presence of 5-hydroxymethylcytosine(5-hmC)marks under inflammatory conditions both in vitro and in vivo.METHODS TET-2 expression was evaluated in parental HT-29 cells and in HT-29 cells expressing low or high levels of Cx43,a putative tumor-suppressor gene whose expression varies in IBD and colorectal cancer,and which has been implicated in the inflammatory process and in tumor onset.The dextran sulfate sodium-induced colitis model was reproduced in BALB/c mice to evaluate the expression of TET-2 and Cx43 under inflammatory conditions in vivo.In addition,archived colon tissue sections from normal,IBD(ulcerative colitis),and sporadic colon adenocarcinoma patients were obtained and evaluated for the expression of TET-2 and Cx43.Expression levels were reported at the transcriptional level by quantitative real-time polymerase chain reaction,and at the translational level by Western blotting and immunofluorescence.RESULTS Under inflammatory conditions,Cx43 and TET-2 expression levels increased compared to noninflammatory conditions.TET-2 upregulation was more pronounced in Cx43-deficient cells.Moreover,colon tissue sections from normal,ulcerative colitis,and sporadic colon adenocarcinoma patients corroborated that Cx43 expression increased in IBD and decreased in adenocarcinoma,compared to tissues from non-IBD subjects.However,TET-2 expression and 5-hmC mark levels decreased in s

关 键 词：DEMETHYLATION Inflammation-induced carcinogenesis Ulcerative colitis Colorectal cancer CONNEXINS 

分 类 号：R735.34[医药卫生—肿瘤]