Expression alteration of long non-coding RNAs and their target genes in the intestinal mucosa of patients with Crohn’s disease

Abstract

BackgroudCD(Crohn's Disease)is a chronic idiopathic inflammatory disorders of the GI tract. It is increasing worldwide and has become a global health problem. The key pathological mechanism for CD occurrence has not been identified, and present treatments are mostly anti-symptom therapy, which has limited efficacy. In this study, we investigate whether lncRNAs are involved in the pathogenesis of CD and how they may regulate the target genes in CD process. MethodsCD patients were diagnosed in Zhongda Hospital of Southeast University between May 2017 and May 2018. Pathological and normal intestinal mucosa were collected and total RNA was extracted the expression of lncRNA and mRNA was profiled and analyzed by using lncRNA and mRNA gene chips. The lncRNAs and mRNAs with significant alternations (≥10 times and P < 0.05) were identified and verified. The co-expressed mRNAs with the differentially expressed lncRNAs were revealed by CNC analysis. The potential regulatory factors were determined by the Ce (cis/tans) mechanism analysis with the use of miRbase, Targetscan, and NCBI database. Finally, the lncRNA-miRNA/TF-mRNA expression network was predicted. ResultsEight lncRNAs were found to be differentially expressed between the pathological mucosa and the normal mucosas in the ileal end. CNC analysis of the differentially expressed lncRNAs revealed fifty co-expressed mRNAs with positive or negative regulation. Base on the mRNAs KEGG pathway analysis, most of them appeared to be involved in cell signaling pathways. Six lncRNAs in the cytoplasm participated in the Ce mechanism, and the rest two lncRNAs in the nucleus participated in the cis/trans regulation mechanism. Finally, ternary relationship of lncRNAs-miRNAs and TFs-mRNAs was obtained by CNC,KEGG enrichment analysis and Ce (trans/cis) analysis. ConclusionThe differential expression of lncRNAs in CD mucosa indicated that lncRNAs were involved in immune reaction. These lncRNAs might contribute to the regulation of intestinal mucosa function through the genetic network of lncRNAs -miRNAs/TFs-mRNAs.