title: miR-122-mediated translational repression of PEG10 and its suppression in human hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC), a primary liver malignancy, is the most common cancer in males and fourth common cancer in females in Taiwan. HCC patients usually have a poor prognosis due to late diagnosis. It has been classified as a complex disease because of the heterogeneous phenotypic and genetic traits of the patients and a wide range of risk factors. Micro (mi)RNAs regulate oncogenes and tumor suppressor genes that are known to be dysregulated in HCC. Several studies have found an association between downregulation of miR-122, a liver-specific miRNA, and upregulation of paternally expressed gene 10 (PEG10) in HCC; however, the correlation between low miR-122 and high PEG10 levels still remains to be defined and require more investigations to evaluate their performance as an effective prognostic biomarker for HCC.
  
  
  
  An in silico approach was used to isolate PEG10, a potential miR-122 target implicated in HCC development. miR-122S binding sites in the PEG10 promoter were evaluated with a reporter assay. The regulation of PEG10 by miR-122S overexpression was examined by quantitative RT-PCR, western blotting, and immunohistochemistry in miR-122 knockout mice and liver tissue from HCC patients. The relationship between PEG10 expression and clinicopathologic features of HCC patients was also evaluated.
  
  
  
  miR-122 downregulated the expression of PEG10 protein through binding to 3'-untranslated region (UTR) of the PEG10 transcript. In miR-122 knockout mice and HCC patients, the deficiency of miR-122 was associated with HCC progression. The expression of PEG10 was increased in 57.3 % of HCC as compared to paired non-cancerous tissue samples. However, significant upregulation was detected in 56.5 % of patients and was correlated with Okuda stage (P = 0.05) and histological grade (P = 0.001).
  
  
  
  miR-122 suppresses PEG10 expression via direct binding to the 3'-UTR of the PEG10 transcript. Therefore, while PEG10 could not be an ideal diagnostic biomarker for HCC but its upregulation in HCC tissue still has predictive value for HCC prognosis.
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.|Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Yu-Chiau
authors.identifier: 0000-0003-1747-2226
authors.initials: YC
authors.lastname: Shyu
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Lee
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Mu-Jie
authors.initials: MJ
authors.lastname: Lu
authors.affiliation: Department of Pathology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.|Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 259, Taiwan.
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.|Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital and University, Keelung 204, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Huang-Yang
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology in Medicine, National Yang Ming University, Taipei 112, Taiwan.
authors.forename: Ann-Ping
authors.initials: AP
authors.lastname: Tsou
authors.affiliation: Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Hsieh
authors.affiliation: Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan. huangts1234@gmail.com.|Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan. huangts1234@gmail.com.|Department of Chinese Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 259, Taiwan. huangts1234@gmail.com.
authors.forename: Ting-Shuo
authors.initials: TS
authors.lastname: Huang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D060787:Neoplasm Grading; D014176:Protein Biosynthesis / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C432965:PEG10 protein, human; D011506:Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000509:alpha-Fetoproteins
keywords: HCC; PEG10; miR122