This study demonstrated, for the first time, that ADAR1 plays an antiviral role against HBV infection by increasing the level of miRNA-122 in hepatocytes.
In order to assess the sensitivity and reliability of these two class of RNAs as marker of hepatitis B or C induced chronic liver disease, we collected plasma samples from 156 chronic hepatitis B or C patients (HBV active n = 112, HBV carrier n = 19, hepatitis C n = 25) and 22 healthy donors and quantified their circulating mRNA for albumin, HP (haptoglobin), CYP2E1 (cytochrome P450, family 2, subfamily E) and ApoA2 (Apolipoprotein A2) in conjunction with microRNA-122, a well established marker for acute and chronic liver injury.
When correlating miRNA expression with clinical parameters we detected significant association between hepatitis B virus (HBV) infection and miR-122 in serum as well as several serum and tissue-miRNAs that correlated with surgery type.
Aim of this study was to investigate the prognostic potential of plasma microRNA-122 levels in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma after hepatic resection or radiofrequency ablation (RFA).
Our study thereby reveals that under the unique condition of high abundance of miR-122 and viral mRNAs and much lower level of miR-122 target in HBV infection, HBV may have evolved to employ the miRNA-mediated virus and host mRNAs network for optimal fitness within hepatocytes.
However, the researches on the accuracy of miR122 detection in chronic viral hepatitis have been inconsistent, leading us to conduct this meta-analysis to systematically summarize the diagnostic value of circulating miR-122 in patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV)-associated chronic viral hepatitis.<b>Methods:</b> A comprehensive literature search (updated to January 30, 2019) in PubMed, Cochrane library, EMBASE, CNKI, Wanfang, and CQVIP databases was performed to identify eligible studies.
Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients.
Serum also contains microRNAs, a class of small non-coding RNAs that play an important role in regulating gene expression. miR-122 is specific to the liver and correlates strongly with liver enzyme levels and necroinflammatory activity, and other microRNAs are correlated with the degree of fibrosis. miR-122 has also been found to be required for hepatitis C virus (HCV) infection, whereas other microRNAs have been shown to play antiviral roles. miR-125a-5p and miR-1231 have been shown to directly target hepatitis B virus (HBV) transcripts, and others are up- or down-regulated in infected individuals.
In cultured cells, HBV gene expression and replication reduces with increased expression of miR-122, and the expression of miR-122 decreases in the presence of HBV infection and replication.
In all, our study revealed that a number of miRNAs were differentially expressed during HBV infection and underscored the potential importance of miR-122 in the infection process.
Collectively, the findings of the present study may provide insight into the mechanistic role of HBV infection in modulating the expression of miR‑122, which targets the 3'UTR of APOBEC2 mRNA, subsequently inducing liver carcinogenesis.
Moreover, there was a significant correlation between serum miR-122 levels and the levels of HBV DNA, hepatitis B e-antigen, and HBV core-related antigen.
In this study, we explored the clinical significance, transcriptional regulation, and direct target of miR-122 in hepatitis B virus (HBV)-associated hepatocellular carcinoma.
Our study suggests that suppression of miR-122 induced by HBV infection, leads to the inactivation of IFN expression, which in turn enhances HBV replication, contributing to viral persistence and hepatocarcinogenesis.
With regard to liver diseases, miR-122 was shown to stimulate hepatitis C virus (HCV) replication through a unique and unusual interaction with two binding sites in the 5'-UTR of HCV genome to mediate the stability of the viral RNA, whereas inhibit the expression and replication of hepatitis B virus (HBV) by a miR-122-cylin G1/p53-HBV enhancer regulatory pathway.
We found that miR-122 expression in liver was significantly down-regulated in patients with HBV infection compared with healthy controls, and the miR-122 levels were negatively correlated with intrahepatic viral load and hepatic necroinflammation.
The miR-122 and miR-22 levels were negatively correlated with tumor size, lymph node metastasis, TNM stage, pathological type, differentiation grade, liver cirrhosis, AFP and HBV DNA, all of which were independent risk factors (p < 0.05).
In contrast, miR-122 expression is reduced in nonalcoholic steatohepatitis (NASH) patients, and in a subset of hepatocellular carcinoma (HCC) patients including hepatitis B virus (HBV) positive patients with highly invasive and metastatic cancer.
Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk.
These findings indicate that the C to A base change of rs4309483 may alter the expression of miR-122, thus providing protective effect from chronic HBV infection but an increased risk for HCC in HBV carriers.
Moreover, we show that hepatitis B virus X protein binds PPARγ and inhibits the transcription of miR-122, whereas hepatitis C viral particles exhibited no significant effect; these findings provide mechanistic insight into reduction of miR-122 in patients with HBV but not with HCV infection.