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Differential expression profile of hepatic circular RNAs in chronic hepatitis B

Autor: Jing-Hua Fan, Yang Tang, Liang Zhang, Xin Lai, Tai-Cheng Zhou, Xiao Li, Jia Wei, L.-J. Chen
Rok vydání: 2018
Předmět:
Zdroj: Journal of Viral Hepatitis. 25:1341-1351
ISSN: 1352-0504
DOI: 10.1111/jvh.12944
Popis: 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.
Databáze: OpenAIRE
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