Differential expression profile of hepatic circular RNA s in chronic hepatitis B

Summary Circ RNA s exert gene regulatory effects by sequestering target micro RNA s (mi RNA s) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circ RNA s in both health and chronic hepatitis B ( CHB ).To identify hepatic circ RNA s associated with CHB , we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB ‐associated circ RNA s and in silico analysis of the circ RNA ‐mi RNA ‐ mRNA pathways. We used quantitative reverse transcription polymerase chain reaction ( qRT ‐ PCR ) to confirm these results. The profiles of hepatic circ RNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circ RNA s identified to be correlated with CHB . Computational analysis of the circ RNA ‐mi RNA ‐ mRNA pathways revealed a large number of mi RNA s (665), which were putatively targeted by the differentially expressed hepatic circ RNA s. Interestingly, four of the predicted CHB ‐related circ RNA ‐mi RNA ‐ mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV ‐associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFβ2 and a negative correlation between hsa_circ_0000650 and miR‐6873‐3p, which hinted that hsa_circ_0000650 interacted with TGFβ2 mediated by miR‐6873‐3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circ RNA s and circ RNA /mi RNA interactions. Thus, circ RNA s have promise as novel mechanisms underlying the pathogenesis and progression of CHB.