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

• Published in: Journal of gastroenterology and hepatology Vol. 28; no. 8; pp. 1410 - 1415
• Main Authors: Sharma, Haveesh, Estep, Michael, Birerdinc, Aybike, Afendy, Arian, Moazzez, Amir, Elariny, Hazem, Goodman, Zachary, Chandhoke, Vikas, Baranova, Ancha, Younossi, Zobair M
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.08.2013; Wiley Subscription Services, Inc
• Subjects: Adipose tissue; Adult; Biopsy; Body Mass Index; Cohort Studies; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Degeneration; Disease Progression; Enzymes; Fatty liver; Fatty Liver - enzymology; Fatty Liver - genetics; Fatty Liver - pathology; Female; Gastrointestinal surgery; Gene Expression Regulation, Enzymologic - genetics; Hepatocytes; Humans; Intra-Abdominal Fat - enzymology; Intra-Abdominal Fat - metabolism; Liver - pathology; Liver diseases; Male; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; mRNA; Necrosis; Non-alcoholic Fatty Liver Disease; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); Obesity; Pathogenesis; Proteins - genetics; Proteins - metabolism; Ribonuclease III - genetics; Ribonuclease III - metabolism; RNA-Binding Proteins; visceral adipose; non-alcoholic fatty liver disease (NAFLD); miRNA; visceral adipose; non-alcoholic steatohepatitis (NASH)
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.12268

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.