Novel hepatic microRNAs upregulated in human nonalcoholic fatty liver disease

Show full item record



Permalink

http://hdl.handle.net/10138/231593

Citation

Soronen , J , Yki-Järvinen , H , Zhou , Y , Sädevirta , S , Sarin , A-P , Leivonen , M , Sevastianova , K , Perttilä , J , Laurila , P-P , Sigruener , A , Schmitz , G & Olkkonen , V M 2016 , ' Novel hepatic microRNAs upregulated in human nonalcoholic fatty liver disease ' , Physiological Reports , vol. 4 , no. 1 , e12661 . https://doi.org/10.14814/phy2.12661

Title: Novel hepatic microRNAs upregulated in human nonalcoholic fatty liver disease
Author: Soronen, Jarkko; Yki-Järvinen, Hannele; Zhou, You; Sädevirta, Sanja; Sarin, Antti-Pekka; Leivonen, Marja; Sevastianova, Ksenia; Perttilä, Julia; Laurila, Pirkka-Pekka; Sigruener, Alexander; Schmitz, Gerd; Olkkonen, Vesa M.
Contributor: University of Helsinki, National Institute for Health and Welfare (THL)
University of Helsinki, Department of Medicine
University of Helsinki, Minerva Foundation
University of Helsinki, Department of Medicine
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, II kirurgian klinikka
University of Helsinki, Clinicum
University of Helsinki, Medicum
Date: 2016
Language: eng
Belongs to series: Physiological Reports
ISSN: 2051-817X
URI: http://hdl.handle.net/10138/231593
Abstract: MicroRNAs (miRNAs) control gene expression by reducing mRNA stability and translation. We aimed to identify alterations in human liver miRNA expression/function in nonalcoholic fatty liver disease (NAFLD). Subjects with the highest (median liver fat 30%, n = 15) and lowest (0%, n = 15) liver fat content were selected from >100 obese patients for miRNA profiling of liver biopsies on microarrays carrying probes for 1438 human miRNAs (a cross-sectional study). Target mRNAs and pathways were predicted for the miRNAs most significantly upregulated in NAFLD, their cell-type-specific expression was investigated by quantitative PCR (qPCR), and the transcriptome of immortalized human hepatocytes (IHH) transfected with the miRNA with the highest number of predicted targets, miR-576-5p, was studied. The screen revealed 42 miRNAs up- and two downregulated in the NAFLD as compared to non-NAFLD liver. The miRNAs differing most significantly between the groups, miR-103a-2*, miR-106b, miR-576-5p, miRPlus-I137*, miR-892a, miR-1282, miR-3663-5p, and miR-3924, were all upregulated in NAFLD liver. Target pathways predicted for these miRNAs included ones involved in cancer, metabolic regulation, insulin signaling, and inflammation. Consistent transcriptome changes were observed in IHH transfected with miR-576-5p, and western analysis revealed a marked reduction of the RAC1 protein belonging to several miR-576-5p target pathways. To conclude, we identified 44 miRNAs differentially expressed in NAFLD versus non-NAFLD liver, 42 of these being novel in the context of NAFLD. The study demonstrates that by applying a novel study set-up and a broad-coverage array platform one can reveal a wealth of previously undiscovered miRNA dysregulation in metabolic disease.
Subject: Hepatocyte, immortalized human hepatocytes, liver biopsy, microarray, microRNA, nonalcoholic fatty liver disease
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
Soronen_et_al_2016_Physiological_Reports.pdf 460.3Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record