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Series GSE59492 Query DataSets for GSE59492
Status Public on Aug 02, 2016
Title Integrative analysis of microRNA and gene expression profiles identifies microRNAs as potential regulators in alcoholic hepatitis
Platform organism synthetic construct
Sample organism Homo sapiens
Experiment type Non-coding RNA profiling by array
Summary Background & aims: The role of microRNAs (miRNAs) in Alcoholic Hepatitis (AH) and their potential as therapeutic targets in liver disease has not been explored yet. This study aims at profiling miRNA in AH and identifying dysregulated miRNAs involved in AH pathophysiology. Methods: miRNA expression arrays were performed in 13 AH, 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples. Genome wide expression profile was retrieved for 12 paired AH and control samples. MiRNA and mRNA expression data was integrated and identified miRNAs were validated in AH samples and in animal models of liver injury. Results: The miRNA array showed 111 upregulated and 66 downregulated miRNAs in AH versus healthy subjects. The comparison of miRNA profile in liver samples from AH among ALD-CH, HCV-CH and NASH-CH identified 18 miRNAs specifically dysregulated in AH. Integrative miRNA and mRNA analysis in AH identified dysregulated miRNAs for which their target genes were also dysregulated. A functional analysis of identified miRNAs and their targets revealed their involvement in the regulation of canonical pathways related to apoptosis, fatty acid metabolism and cell cycle among others. miRNAs expression (miR-182, miR-21, miR-155, miR-214, miR-432, miR-422a) was validated in an independent cohort of AH. MiR-182 expression correlated with cholestasis, disease severity and short-term mortality. Moreover, miR-182 expression is associated to cholestasis with ductular reaction but not to fibrosis and inflammation in animal models of liver injury. Conclusions: AH is characterized by an important dysregulation of miRNA expression with a unique miRNA profile. MiRNAs specifically expressed in AH are associated to cholestasis… Uncovered miRNAs are involved in important pathophysiological features in AH suggesting ta regulation of he role of miRNAs in the regulation of AH, and highlight miR-182 as a potential regulator of its pathophysiology.
 
Overall design miRNA expression arrays were performed in 13 AH(Alcoholic hepatitis), 5 alcohol liver disease-induced cirrhosis (ALD-CH), 5 nonalcoholic steatohepatitis induced cirrhosis (NASH-CH), 4 HCV-induced cirrhosis (HCV-CH) and 6 non-injured liver control samples(CTRL).
 
Contributor(s) Lozano JJ, Blaya D, Sancho-Bru P
Citation(s) 27196584
Submission date Jul 16, 2014
Last update date Jul 27, 2018
Contact name Juanjo Lozano
E-mail(s) juanjo.lozano@ciberehd.org
Organization name CIBEREHD
Department Plataforma de Bioinformatica
Street address C/ Rosselló 153
City Barcelona
ZIP/Postal code 08036
Country Spain
 
Platforms (1)
GPL16384 [miRNA-3] Affymetrix Multispecies miRNA-3 Array
Samples (33)
GSM1438158 Biopsy Liver sample: CA.12_.miRNA.3_0..CEL
GSM1438161 Biopsy Liver sample: CA.16_.miRNA.3_0..CEL
GSM1438162 Biopsy Liver sample: CA.37_.miRNA.3_0..CEL
Relations
BioProject PRJNA255423

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE59492_RAW.tar 48.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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