Circular RNA expression profile in peripheral blood mononuclear cells from Crohn disease patients.

Abstract

Crohn disease (CD) is a multifactorial autoimmune disease which is characterized by chronic and recurrent gastrointestinal tract inflammatory disorder. However, the molecular mechanisms of CD remain unclear. Increasing evidences have demonstrated that circular RNAs (circRNAs) participate in the pathogenesis of a variety of disease and were considered as ideal biomarkers in human disease. This study aimed to investigate circRNA expression profiles and detect new biomarkers in inflammatory bowel disease (IBD). Differentially expression of circRNAs between CD and HCs (health controls) were screened by microarray analysis. Peripheral blood mononuclear cells (PBMCs) from 5 CD patients and 5 HCs were included in the microarray analysis. Then, the differences were validated by quantitative polymerase chain reaction (qPCR) following reverse transcription polymerase chain reaction (RT-PCR) in the patients of CD and sex- and age-matched HCs. The most differential expressed circRNA was further validated in ulcerative colitis (UC) patients. Statistical significance between CD, UC, and HCs was analyzed by Student t test for unpaired samples or one-way analysis of variance (ANOVA). Diagnostic value of each circRNA was assessed by receiver operating characteristic (ROC) curve. We identified 155 up-regulated circRNAs and 229 down-regulated ones by microarray analysis in PBMCs from CD patients compared with HCs. Besides, 4 circRNAs (092520, 102610, 004662, and 103124) were significantly up-regulated validated by RT-PCR and qPCR between CD and HCs. ROC curve analysis suggested important values of circRNAs (092520, 102610, 004662, and 103124) in CD diagnosis, with area under the curve (AUC) as 0.66, 0.78, 0.85, and 0.74, respectively. Then, we further identified that the relative expression levels of circRNA_004662 was upregulated significantly in CD patients compared with UC patients. Herein, the upregulation of the 4 circRNAs (092520, 102610, 004662, or 103124) in PBMCs can be served as potential diagnostic biomarkers of CD, and circRNA_004662 might be a novel candidate for differentiating CD from UC. Moreover, a circRNA–microRNA-mRNA network predicted that circRNA_004662 appeared to be correlated with mammalian target of rapamycin (mTOR) pathway.