Differential expression profile of hepatic circular RNAs in chronic hepatitis B

Abstract

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.

Circular RNA hsa_circ_0004812 impairs IFN-induced immune response by sponging miR-1287-5p to regulate FSTL1 in chronic hepatitis B

“…These studies highlighted that circRNA might be used as a therapeutic biomarker in the development of CHB. In 2018, Zhou and colleagues have reported that circ_0004812 is one of the top ten circRNAs significantly up-regulated in CHB compared to normal controls [15] Interestingly, we also identified that circ_0004812 was upregulated in CHB patients as well as HBV-infected hepatoma cell lines.…”

“…In 2018, Zhou and colleagues have reported that circ_ 0004812 is one of the top ten circRNAs significantly upregulated in CHB compared to normal controls [15]. However, the underlying mechanisms of circ_0004812 in the CHB patients are still unclear.…”

Emerging roles of circRNA in formation and progression of cancer

“…The expression of hsa_circ_0005986 is lower in HCC tissues compared with adjacent normal tissues as a tumor suppressor in HCC carcinogenesis [42] . Especially, a total of 99 dysregulated circRNAs are identified to be associated with chronic hepatitis B (CHB) by circRNA/miRNA regulatory axes [43] [44] . Among them, miR-122 is one of the most abundant miRNAs in the liver and plays a central role in the HCV life cycle [44] .…”

Molecular mechanisms of circular RNAs, transforming growth factor‐β, and long noncoding RNAs in hepatocellular carcinoma

“…CircRNAs are thought to modulate the HCV or HBV infection, via influencing hepatocarcinogenesis. A previous study found that 99 circRNAs were dysregulated and were associated with chronic hepatitis B (CHB) . To predict the roles of the circRNAs in CHB, CircRNA/miRNA interaction networks were constructed.…”