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

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.

journal_name

J Gastroenterol Hepatol

journal_title

Journal of gastroenterology and hepatology

authors

Sharma H,Estep M,Birerdinc A,Afendy A,Moazzez A,Elariny H,Goodman Z,Chandhoke V,Baranova A,Younossi ZM

doi

10.1111/jgh.12268

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

1410-5

issue

eissn

0815-9319

issn

1440-1746

journal_volume

pub_type

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