Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease

Authors

  • Haveesh Sharma,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
    2. Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, Virginia, USA
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  • Michael Estep,

    1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
    2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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  • Aybike Birerdinc,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
    2. Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, Virginia, USA
    3. Center for the Study of Chronic Metabolic Diseases, College of Science, George Mason University, Fairfax, Virginia, USA
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  • Arian Afendy,

    1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
    2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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  • Amir Moazzez,

    1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
    2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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  • Hazem Elariny,

    1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
    2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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  • Zachary Goodman,

    1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
    2. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
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  • Vikas Chandhoke,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
    2. Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, Virginia, USA
    3. Center for the Study of Chronic Metabolic Diseases, College of Science, George Mason University, Fairfax, Virginia, USA
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  • Ancha Baranova,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
    2. Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, Virginia, USA
    3. Center for the Study of Chronic Metabolic Diseases, College of Science, George Mason University, Fairfax, Virginia, USA
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  • Zobair M Younossi

    Corresponding author
    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia, USA
    • Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia, USA
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Correspondence

Dr Zobair M Younossi, Department of Medicine, Inova Fairfax Hospital, Inova Health System, VCU-Inova Campus, Beatty Center for Integrated Research, 3300 Gallows Road, Falls Church, VA 22042, USA. Email: zobair.younossi@inova.org

Abstract

Background and Aim

Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA.

Methods

Total RNAs were extracted from visceral adipose tissue (VAT) samples collected from patients undergoing bariatric surgery. All patients had biopsy-proven NAFLD (NASH patients [n = 12] and non-NASH NAFLD [n = 12]). For each patient, we profiled mRNA levels for three miRNA processing elements (Drosha, DGCR8, and Dicer1) and seven pri-miRNAs (pri-miR-125b-2, pri-miR-16-2, pri-miR-26a-1, pri-miR-26a-2, pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3).

Results

Expression of Dicer1, Drosha and DGCR8 was significantly increased within the NASH cohort along with expression of pri-miR-7-1. The presence of focal necrosis on the liver biopsy correlated significantly with levels of Dicer1 and DGRC8. Both NASH and ballooning degeneration of hepatocytes correlated negatively with the expression levels of hsa-miR-125b. Histologic NASH correlated positively with the expression levels of pri-miR-16-2 and pri-miR-7-1. The presence of the hepatocyte's ballooning degeneration in the liver biopsy correlated positively with pri-miR-26a-1 and pri-miR-7-1. The expression profile of pri-miR-125b-2 also correlated positively with body mass index.

Conclusions

Our findings support the hypothesis that VAT-derived miRNA may contribute to the pathogenesis of NASH in obese patients.

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