title: Hepatitis B viral RNA directly mediates down-regulation of the tumor suppressor microRNA miR-15a/miR-16-1 in hepatocytes.
abstract: Hepatitis B virus (HBV) is a key risk factor for the development of hepatocellular carcinoma (HCC). Recent work suggests a functional link between HCC and microRNA expression, but the mechanism underlying the functional interaction between microRNA and HBV infection has remained largely elusive. Here we present evidence that the microRNA machinery serves as a defense system against HBV infection, which, in turn, reprograms the expression of specific microRNAs. We demonstrate a critical role of miR-15a/miR-16-1 in this functional interplay between microRNA and HBV infection, but in contrast to various indirect mechanisms mediated by viral proteins, we unexpectedly found that the HBx transcript directly triggers the down-regulation of miR-15a/miR-16-1 via the microRNA targeting sequences in the viral RNA. Because miR-15a and miR-16-1 are well known tumor suppressor microRNAs in multiple human cancers, our findings raise the intriguing possibility that viral RNA-mediated down-regulation of specific tumor suppressor microRNAs may contribute to HCC development in HBV-infected cells.
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
authors: Yanling
authors: Y
authors: Wang
authors: Li
authors: L
authors: Jiang
authors: Xiong
authors: X
authors: Ji
authors: Bo
authors: B
authors: Yang
authors: Yi
authors: Y
authors: Zhang
authors: Xiang-Dong
authors: XD
authors: Fu
mesh_terms: D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000235:genetics
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: Gene Regulation; Hepatitis Virus; MicroRNA; Tumor Suppressor Gene; Viral DNA
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