These authors contributed equally to this paper as first authors.
Metabolic and Steatohepatitis
Circulating MicroRNAs as potential biomarkers for alcoholic steatohepatitis
Article first published online: 20 MAY 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 33, Issue 8, pages 1257–1265, September 2013
How to Cite
Liver Int. 2013: 33: 1257–1265
- Issue published online: 11 AUG 2013
- Article first published online: 20 MAY 2013
- Accepted manuscript online: 29 APR 2013 03:14AM EST
- Manuscript Accepted: 4 APR 2013
- Manuscript Received: 19 OCT 2012
- National Natural Science Foundation of China. Grant Number: Project 81 000 169
- Excellent Young Investigator Foundation of Health Bureau of Zhejiang Province. Grant Number: Project 2010QNA011
- Excellent Young Investigator Natural Science Foundation of Zhejiang province. Grant Number: Project R2110159
- National Technology Supporting Project. Grant Number: 2008BAI52B03
- serum miRNA
To investigate serum miRNA profile in alcoholic steatohepatitis (ASH), evaluate its effect as non-invasive diagnostic tool and to study its targets' function.
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.
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.
We have reported a unique serum miRNA pattern for non-invasive diagnosis of ASH and provided data reservoir for miRNA and downstream targets exploration.