title: Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers.
abstract: BACKGROUND
  It is known that malignant transformation to hepatocellular carcinoma (HCC) occurs at a higher frequency in hepatocellular adenoma (HCA) from type I glycogen storage disease (GSD I) compared to HCA from other etiologies. In this study, we aimed to identify differentially expressed miRNAs in GSD Ia HCA as candidates that could serve as putative biomarkers for detection of GSD Ia HCA and/or risk assessment of malignant transformation.
  
  
  METHODS
  Utilizing massively parallel sequencing, the miRNA profiling was performed for paired adenomas and normal liver tissues from seven GSD Ia patients. Differentially expressed miRNAs were validated in liver tumor tissues, HCC cell lines and serum using quantitative RT-PCR.
  
  
  RESULTS
  miR-34a, miR-34a, miR-224, miR-224, miR-424, miR-452 and miR-455-5p were found to be commonly deregulated in GSD Ia HCA, general population HCA, and HCC cell lines at compatible levels. In comparison with GSD Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b-5p, and miR-214 were more significant in HCC cell lines. Furthermore, serum level of miR-130b in GSD Ia patients with HCA was moderately higher than that in either GSD Ia patients without HCA or healthy individuals.
  
  
  CONCLUSIONS
  We make the first observation of distinct miRNA deregulation in HCA associated with GSD Ia. We also provide evidence that miR-130b could serve as a circulating biomarker for detection of GSD Ia HCA. This work provides prominent candidate miRNAs worth evaluating as biomarkers for monitoring the development and progress of liver tumors in GSD Ia patients in the future.
authors.affiliation: National Center for Genome Medicine, Academia Sinica, Taipei, Taiwan.
authors.forename: Li-Ya
authors.initials: LY
authors.lastname: Chiu
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.forename: Tzu-Po
authors.initials: TP
authors.lastname: Chuang
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Tang
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Liu
authors.forename: Deeksha
authors.initials: D
authors.lastname: Bali
authors.forename: Dwight
authors.initials: D
authors.lastname: Koeberl
authors.forename: Stephanie
authors.initials: S
authors.lastname: Austin
authors.forename: Keri
authors.initials: K
authors.lastname: Boyette
authors.forename: David A
authors.initials: DA
authors.lastname: Weinstein
authors.forename: Elaine
authors.initials: E
authors.lastname: Murphy
authors.forename: Adam
authors.initials: A
authors.lastname: Yao
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Li
mesh_terms: D018248:Adenoma, Liver Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005953:Glycogen Storage Disease Type I / Q000150:complications* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C554019:MIRN130 microRNA, human; D035683:MicroRNAs