title: Circulating MicroRNAs as potential biomarkers for alcoholic steatohepatitis.
abstract: OBJECTIVE
  To investigate serum miRNA profile in alcoholic steatohepatitis (ASH), evaluate its effect as non-invasive diagnostic tool and to study its targets' function.
  
  
  METHODS
  Microarray and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were utilized to detect serum miRNAs pattern in a rat ASH model, followed by target prediction with bioinformatics calculation. The functions and pathways of miRNAs' targets were analysed using databases of Gene Ontology and KEGG. The association between dysregulated miRNAs and genes was assessed by MiR-Gene Network. Five top dysregulated miRNAs were also verified in humans.
  
  
  RESULTS
  Eight up-regulated and three down-regulated serum miRNAs were selected as an accurate molecular signature in distinguishing ASH from control. For up-regulated miRNAs, 122 GO and 144 KEGG pathways were significantly enriched, including apoptosis, lipid metabolic process, PPAR signalling pathway. For down-regulated miRNAs, 86 GO and 104 KEGG pathways were enriched, including fatty acid metabolism and insulin signalling pathway. Besides, Ccdc117, Gcom1, Zmynd11 and Zfp423 were found at top list as under common regulation of maximum miRNAs. Moreover, miR-214 had the highest degree of 63 among all miRNAs, followed by miR-203 and miR-539. Similarly, Stat3 and Lyn showed the highest degree of 5 among all downstream targets. All significance analysis of microarrays (SAM) revealed that five top dysregulated miRNAs showed the same tendency in humans.
  
  
  CONCLUSIONS
  We have reported a unique serum miRNA pattern for non-invasive diagnosis of ASH and provided data reservoir for miRNA and downstream targets exploration.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yi-peng
authors.initials: YP
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.forename: Zun
authors.initials: Z
authors.lastname: Xiang
authors.forename: Shao-hua
authors.initials: SH
authors.lastname: Chen
authors.forename: You-ming
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods; D035683:MicroRNAs / Q000097:blood*; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
keywords: miR-21; microarray; qRT-PCR; serum miRNA