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Hepatitis B Virus-Encoded MicroRNA (HBV-miR-3) Regulates Host Gene PPM1A Related to Hepatocellular Carcinoma

Author(s):

Tanit Chavalit, Pattaraporn Nimsamer, Kritsada Khongnomnan, Songtham Anuntakarun, Suthat Saengchoowong, Pisit Tangkijvanich and Sunchai Payungporn*   Pages 1 - 7 ( 7 )

Abstract:


Background: Hepatitis B is a liver infected disease caused by the hepatitis B virus (HBV) that can become chronic and develop to the hepatocellular carcinoma. HBV was classified as a double-stranded DNA virus. Currently, there is a report showing that HBV virus-encoded miRNA called HBV-miR-3 which control in the replication of HBV. However, the regulation of HBV-miR-3 to host cells remains unclear.

Objective: This study aimed to investigate the regulation of HBV-miR-3 in host gene target which related to chronic HBV infection and HCC process.

Method: In this study, we analysed the read count of HBV-miR-3 from next-generation sequencing of chronic hepatitis patients in Pegylated interferon alpha-2a (PEG-IFN-α-2a) treatment. To understanding the regulation of HBV-miR-3 in host cells, the HBV-miR-3 recognition sizes were predicted in host target genes using miRDB. The effect of HBV-miR-3 in host cells were examined using qPCR and 3′ UTR dual luciferase assay.

Results: The read count of HBV-miR-3 was found in chronic hepatitis patients before treatment. Moreover, the decreasing of HBV-miR-3 was correlated response group of chronic hepatitis patients after treatment. On the other hand, the abundance of HBV-miR-3 showed no difference in non-response group of chronic patients after PEG-IFN-α-2a treatment. To study the role of HBV-miR-3 in patients, the four HBV-miR-3 target regions from Protein phosphatase 1A (PPM1A) and DIX domain containing 1 (DIXDC1) were identified in the human genome using miRDB. Interestingly, we found that HBV-miR-3 hybridized with PPM1A mRNA. The mRNA expression from RT-qPCR showed no different between HepG2 transfected with pSilencer_scramble or pSilencer_HBV-miR-3. However, the reporter assay showed that PPM1A mRNA was suppressed by HBV-miR-3. The protein expression of PPM1A showed decreasing in cell overexpressing HBV-miR-3. Finally, the HBV-miR-3 can promote cell proliferation in cell overexpressing HBV-miR-3.

Conclusion: This study is the first report showed the HBV encoded miRNA can regulate host gene expression. HBV-miR-3 silenced PPM1A by inhibiting the translation process of PPM1A. The downregulation of PPM1A promotes cell proliferation related to HCC development.

Keywords:

HBV-miR-3, miRNA, PPM1A, HCC, HepG2 cells, infection

Affiliation:

Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok



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