title: microRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection.
abstract: Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917), and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV-associated HCC may signify an important role for HCV replication late in the progression to malignancy.
authors.affiliation: Departments of Medicine and Microbiology & Immunology and the Lineberger Comprehensive Cancer Center, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Spaniel
authors.forename: Masao
authors.initials: M
authors.lastname: Honda
authors.forename: Sara R
authors.initials: SR
authors.lastname: Selitsky
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamane
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shimakami
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lanford
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
mesh_terms: D000368:Aged; D000818:Animals; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D002679:Pan troglodytes
chemical_list: C531907:MIRN122 microRNA, human; C546177:MIRN191 microRNA, human; D035683:MicroRNAs; D007372:Interferons