Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers
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  • 作者:Li-Ya Chiu (1) <br> Priya S. Kishnani (2) <br> Tzu-Po Chuang (3) (4) <br> Cheng-Yang Tang (1) <br> Cheng-Yuan Liu (5) <br> Deeksha Bali (2) <br> Dwight Koeberl (2) <br> Stephanie Austin (2) <br> Keri Boyette (2) <br> David A. Weinstein (6) <br> Elaine Murphy (7) <br> Adam Yao (1) (8) <br> Yuan-Tsong Chen (2) (8) <br> Ling-Hui Li (1) (8) <br>
  • 关键词:Glycogen storage disease ; Hepatocellular adenoma ; Hepatocellular carcinoma ; miRNA ; miR ; 130b
  • 刊名:Journal of Gastroenterology
  • 出版年:2014
  • 出版时间:August 2014
  • 年:2014
  • 卷:49
  • 期:8
  • 页码:1274-1284
  • 全文大小:1,300 KB
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  • 作者单位:Li-Ya Chiu (1) <br> Priya S. Kishnani (2) <br> Tzu-Po Chuang (3) (4) <br> Cheng-Yang Tang (1) <br> Cheng-Yuan Liu (5) <br> Deeksha Bali (2) <br> Dwight Koeberl (2) <br> Stephanie Austin (2) <br> Keri Boyette (2) <br> David A. Weinstein (6) <br> Elaine Murphy (7) <br> Adam Yao (1) (8) <br> Yuan-Tsong Chen (2) (8) <br> Ling-Hui Li (1) (8) <br><br>1. National Center for Genome Medicine, Academia Sinica, Taipei, Taiwan <br> 2. Division of Pediatric Medical Genetics, Duke University Medical Center, Durham, NC, USA <br> 3. Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan <br> 4. Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan <br> 5. Life Technology Taiwan Branch, Taipei, Taiwan <br> 6. Glycogen Storage Disease Program, University of Florida College of Medicine, Gainesville, FL, USA <br> 7. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK <br> 8. Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan <br>
  • ISSN:1435-5922
文摘
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. Conclusion 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.

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