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Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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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Acknowledgments

The authors would like to thank the participants and their families. We also like to acknowledge the funding support from Institute of Biomedical Sciences, Academia Sinica (to Y.-T. Chen and L.-H. Li) and Academia Sinica (GMM to Y.-T. Chen).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. National Center for Genome Medicine, Academia Sinica, Taipei, Taiwan

    Li-Ya Chiu, Cheng-Yang Tang, Adam Yao & Ling-Hui Li

  2. Division of Pediatric Medical Genetics, Duke University Medical Center, Durham, NC, USA

    Priya S. Kishnani, Deeksha Bali, Dwight Koeberl, Stephanie Austin, Keri Boyette & Yuan-Tsong Chen

  3. Molecular Medicine Program, Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Tzu-Po Chuang

  4. Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan

    Tzu-Po Chuang

  5. Life Technology Taiwan Branch, Taipei, Taiwan

    Cheng-Yuan Liu

  6. Glycogen Storage Disease Program, University of Florida College of Medicine, Gainesville, FL, USA

    David A. Weinstein

  7. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK

    Elaine Murphy

  8. Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan

    Adam Yao, Yuan-Tsong Chen & Ling-Hui Li

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  1. Li-Ya Chiu
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  2. Priya S. Kishnani
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  11. Elaine Murphy
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Correspondence to Ling-Hui Li.

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Chiu, LY., Kishnani, P.S., Chuang, TP. et al. Identification of differentially expressed microRNAs in human hepatocellular adenoma associated with type I glycogen storage disease: a potential utility as biomarkers. J Gastroenterol 49, 1274–1284 (2014). https://doi.org/10.1007/s00535-013-0890-2

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  • DOI: https://doi.org/10.1007/s00535-013-0890-2

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