title: Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia 22042, USA.
authors.forename: Haveesh
authors.initials: H
authors.lastname: Sharma
authors.forename: Michael
authors.initials: M
authors.lastname: Estep
authors.forename: Aybike
authors.initials: A
authors.lastname: Birerdinc
authors.forename: Arian
authors.initials: A
authors.lastname: Afendy
authors.forename: Amir
authors.initials: A
authors.lastname: Moazzez
authors.forename: Hazem
authors.initials: H
authors.lastname: Elariny
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.forename: Vikas
authors.initials: V
authors.lastname: Chandhoke
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
mesh_terms: D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D005234:Fatty Liver / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009336:Necrosis; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism*
chemical_list: C474043:DGCR8 protein, human; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: miRNA; non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis (NASH); visceral adipose