Chimiothérapie : Libre accès
Libre accès

Abstrait

A Novel Strategy to Identify mRNA 3′ UTR and mRNA Level Difference in Crohn’s Disease

Tuo Hu, Hua-shan Liu, Chi Zhou, Xian-rui Wu, Yu-feng Chen, Xuan-hui Liu, Xiao-wen He, Yi-feng Zou, Xiao-sheng He, Xiao-jian Wu, Ping Lan and Jia Ke

Abstract Background and Aims: Crohn’s disease (CD) is a chronic and refractory intestinal inflammatory disease. The 3′ untranslated region (3′ UTR) of mRNA transcript can regulate its own translational process post-transciptionally, and its role in CD remains unclear. The aim of this study was to identify the critical genes influencing CD phenotype via the regulation of mRNA 3′ UTR. Methods: Isoform Structural Change Model (IsoSCM) was used to evaluate the length of 3′ UTR of the whole transciptome from a RNA-seq based online CD database. Correlations between 3′ UTR length status and mRNA level were analyzed by Spearman coefficients. Correlated genes list was overlapped with published critical CD related gene list. Univariate and multivariate analysis were performed to identify the genes associated with CD phenotype. Results: Compared with normal control, 3′ UTR of 34192 genes were shortened and 57389 were lengthened among 432784 genes in CD patients. The 3′ UTR changes of 255 genes were found significantly correlated with their mRNA level. Furthermore, 8 overlapped genes were shared by above 255 correlated genes and known CD related gene list (ABCB1, FAF1, TUT2, IL27, JAK2, LTB, NAGLU and PTPN2). The mRNA level of ABCB1 and JAK2, and shortened 3′ UTR length of JAK2 transcript were found to be correlated with deep ulcer in CD patients by univariate and multivariate analysis. Conclusions: The 3′ UTR changes of CD related genes were confirmed to be related to the phenotype of CD. Our findings may provide further insight into the epigenetic mechanisms and therapeutic strategies for CD.