Differential expression profile of hepatic circular RNAs in chronic hepatitis B. Issue 11 (11th July 2018)

• Record Type: Journal Article
• Authors: Zhou, T.‐C.; Li, X.; Chen, L.‐J.; Fan, J.‐H.; Lai, X.; Tang, Y.; Zhang, L.; Wei, J.
• Is Part Of: Journal of viral hepatitis. Volume 25:Issue 11(2018)
• Page Start: 1341
• Page End: 1351
• Publication Date: 2018-07-11
• Subjects: chronic hepatitis B -- circular RNA -- expression profile -- microRNA; Hepatitis, Viral -- Periodicals; Hepatitis, Viral, Animal; Hepatitis, Viral, Human; 616.3623
• DOI: 10.1111/jvh.12944
• Languages: English
• ISSNs: 1352-0504

Abstract

Summary: CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) 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 circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs 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 circRNAs and in silico analysis of the circRNA‐miRNA‐mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT‐PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA‐miRNA‐mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB‐related circRNA‐miRNA‐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 circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.