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Journal of Gastroenterology

, Volume 49, Issue 8, pp 1274–1284 | Cite as

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

  • Li-Ya Chiu
  • Priya S. Kishnani
  • Tzu-Po Chuang
  • Cheng-Yang Tang
  • Cheng-Yuan Liu
  • Deeksha Bali
  • Dwight Koeberl
  • Stephanie Austin
  • Keri Boyette
  • David A. Weinstein
  • Elaine Murphy
  • Adam Yao
  • Yuan-Tsong Chen
  • Ling-Hui Li
Original Article—Liver, Pancreas, and Biliary Tract

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.

Keywords

Glycogen storage disease Hepatocellular adenoma Hepatocellular carcinoma miRNA miR-130b 

Notes

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.

Supplementary material

535_2013_890_MOESM1_ESM.doc (318 kb)
Supplementary material 1 (DOC 318 kb)

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Copyright information

© Springer Japan 2013

Authors and Affiliations

  • Li-Ya Chiu
    • 1
  • Priya S. Kishnani
    • 2
  • Tzu-Po Chuang
    • 3
    • 4
  • Cheng-Yang Tang
    • 1
  • Cheng-Yuan Liu
    • 5
  • Deeksha Bali
    • 2
  • Dwight Koeberl
    • 2
  • Stephanie Austin
    • 2
  • Keri Boyette
    • 2
  • David A. Weinstein
    • 6
  • Elaine Murphy
    • 7
  • Adam Yao
    • 1
    • 8
  • Yuan-Tsong Chen
    • 2
    • 8
  • Ling-Hui Li
    • 1
    • 8
  1. 1.National Center for Genome Medicine, Academia SinicaTaipeiTaiwan
  2. 2.Division of Pediatric Medical GeneticsDuke University Medical CenterDurhamUSA
  3. 3.Molecular Medicine Program, Taiwan International Graduate ProgramInstitute of Biomedical Sciences, Academia SinicaTaipeiTaiwan
  4. 4.Institute of Biochemistry and Molecular Biology, School of Life SciencesNational Yang-Ming UniversityTaipeiTaiwan
  5. 5.Life Technology Taiwan BranchTaipeiTaiwan
  6. 6.Glycogen Storage Disease ProgramUniversity of Florida College of MedicineGainesvilleUSA
  7. 7.Charles Dent Metabolic UnitNational Hospital for Neurology and NeurosurgeryLondonUK
  8. 8.Institute of Biomedical Sciences, Academia SinicaTaipeiTaiwan

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