lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn’s disease  

作　　者：Na Li Rui-Hua Shi 

机构地区：[1]Medical School of Southeast University,Nanjing 210009,Jiangsu Province,China [2]Department of Gastroenterology,Zhongda Hospital,Affiliated Hospital of Southeast University,Nanjing 210009,Jiangsu Province,China [3]Department of Biomedical Science,Mercer University School of Medicine,Savannah,GA 31404,United States

出　　处：《World Journal of Gastroenterology》2020年第5期478-498,共21页世界胃肠病学杂志（英文版）

基　　金：Supported by Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_0174

摘　　要：BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD) is rising in many countries. The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease. Previous studies showed that long noncoding RNAs(lncRNAs) could be involved in autoimmune diseases including CD, but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD, and to characterize their pathogenic role(s) and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing, and the top candidate genes were validated in an expanded cohort by real-time PCR. The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis, and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection, real-time PCR,Western blotting analysis, flow cytometry, and cell migration and invasion assays. Finally, these findings were confirmed in vivo using a CD animal model.RESULTS The 3’ end of lncRNACNN3-206 and the 3’ UTR of Caspase10 contain highaffinity miR212 binding sites. lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients. Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis, migration and invasion in intestinal epithelial cells. Knockdown oflncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis. lncRNACNN3-206 could be a therapeutic target for CD treatment.

关 键 词：Crohn’s disease MICROARRAY lncRNACNN3-206 Gene regulation Cell migration and invasion miR-212 

分 类 号：R73[医药卫生—肿瘤]