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MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma.

ABSTRACT: Hepatitis B virus (HBV) infection is known as a serious problem in the domain of public health and approximately 350 million people across the world are affected with this infectious disease. As well, microRNAs are recognized as a type of small non-coding RNAs that can be widely used as a diagnostic biomarker and prognosis method of special diseases. In this respect, microRNA-122 or miR-122 can play a significant role in the pathogenesis of several hepatic diseases. Given the importance of microRNA-122 in the liver as well as its pathology, this study focused on the potential functions of microRNA-122 in pathogenesis, diagnosis, and treatment of HBV infection. In this regard, the findings of previous studies had indicated that expression of microRNA-122 in patients with HBV infection could be significantly deregulated. The results of this study were consistent with the idea that diagnosis and treatment of this infectious disease using microRNA-122 could be an efficient method.

SUBMITTER: Mahmoudian-Sani MR

PROVIDER: S-EPMC6657334 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma.

Mahmoudian-Sani Mohammad Reza MR Asgharzade Samira S Alghasi Arash A Saeedi-Boroujeni Ali A Adnani Sadati Seyed Jafar SJ Moradi Mohammad Taghi MT

Journal of gastrointestinal oncology 20190801 4

Hepatitis B virus (HBV) infection is known as a serious problem in the domain of public health and approximately 350 million people across the world are affected with this infectious disease. As well, microRNAs are recognized as a type of small non-coding RNAs that can be widely used as a diagnostic biomarker and prognosis method of special diseases. In this respect, microRNA-122 or miR-122 can play a significant role in the pathogenesis of several hepatic diseases. Given the importance of micro ...[more]

PMID: 31392060

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Project description:The molecular mechanisms of liver pathology and clinical disease in hepatitis E virus (HEV) infection remain unclear. MicroRNAs (miRNAs) are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using HEV genotype 1 (HEV-1), HEV-2, HEV-3, and HEV-4 sequences showed that the majority of genomes (203/222) harbor at least one miR-122/microRNA-122-3p (miR-122*) target site. Interestingly, HEV-1 genomes showed a highly (97%) conserved miR-122 target site in the RNA-dependent RNA polymerase (RdRp) region (RdRpc). We analyzed the significance of miR-122 target sites in HEV-1/HEV-3 (HEV-1/3) genomes by using a replicon-based cell culture system. HEV infection did not change the basal levels of miR-122 in hepatoma cells. However, transfection of these cells with miR-122 mimics enhanced HEV-1/3 replication and depletion of miR-122 with inhibitors led to suppression of HEV-1/3 replication. Mutant HEV-1 replicons with an altered target RdRpc sequence (CACTCC) showed a drastic decrease in virus replication, whereas introduction of alternative miR-122 target sites in mutant replicons rescued viral replication. There was enrichment of HEV-1 RNA and miR-122 molecules in RNA-induced silencing complexes in HEV-infected cells. Furthermore, pulldown of miR-122 molecules from HEV-infected cells resulted in pulldown of HEV genomic RNA along with miR-122 molecules. These observations indicate that miR-122 facilitates HEV-1 replication, probably via direct interaction with a target site in the viral genome. The positive role of miR-122 in viral replication presents novel opportunities for antiviral therapy and management of hepatitis E.IMPORTANCE Hepatitis E is a problem in both developing and developed countries. HEV infection in most patients follows a self-limited course; however, 20% to 30% mortality is seen in infected pregnant women. HEV superinfections in patients with chronic hepatitis B or hepatitis C virus infections are associated with adverse clinical outcomes, and both conditions warrant therapy. Chronic HEV infections in immunocompromised transplant recipients are known to rapidly progress into cirrhosis. Currently, off-label use of ribavirin (RBV) and polyethylene glycol-interferon (PEG-IFN) as antiviral therapy has shown promising results in both acute and chronic hepatitis E patients; however, the teratogenicity of RBV limits its use during pregnancy, while alpha IFN (IFN-α) increases the risk of transplant rejections. Experimental data determined with genotype 1 virus in the current study show that miR-122 facilitates HEV replication. These observations present novel opportunities for antiviral therapy and management of hepatitis E.

Dataset Information

MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma.

Publications

MicroRNA-122 in patients with hepatitis B and hepatitis B virus-associated hepatocellular carcinoma.

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