MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 DiabetesReportar como inadecuado




MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genomics

, 2:54

First Online: 18 August 2009Received: 02 October 2008Accepted: 18 August 2009

Abstract

BackgroundMicroRNAs miRNAs are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes T2D is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains.

MethodsWe used a miRNA microarray platform to measure global miRNA expression in two insulin-target tissues: liver and adipose tissue from inbred rats of spontaneously diabetic Goto-Kakizaki GK and normoglycaemic Brown-Norway BN strains which are extensively used in genetic studies of T2D. MiRNA data were integrated with gene expression data from the same rats to investigate how differentially expressed miRNAs affect the expression of predicted target gene transcripts.

ResultsThe expression of 170 miRNAs was measured in liver and adipose tissue of GK and BN rats. Based on a p-value for differential expression between GK and BN, the most significant change in expression was observed for miR-125a in liver FC = 5.61, P = 0.001, Padjusted= 0.10; this overexpression was validated using quantitative RT-PCR FC = 13.15, P = 0.0005. MiR-125a also showed over-expression in the GK vs. BN analysis within adipose tissue FC = 1.97, P = 0.078, Padjusted= 0.99, as did the previously reported miR-29a FC = 1.51, P = 0.05, Padjusted= 0.99. In-silico tools assessing the biological role of predicted miR-125a target genes suggest an over-representation of genes involved in the MAPK signaling pathway. Gene expression analysis identified 1308 genes with significantly different expression between GK and BN rats Padjusted < 0.05: 233 in liver and 1075 in adipose tissue. Pathways related to glucose and lipid metabolism were significantly over-represented among these genes. Enrichment analysis suggested that differentially expressed genes in GK compared to BN included more predicted miR-125a target genes than would be expected by chance in adipose tissue FDR = 0.006 for up-regulated genes; FDR = 0.036 for down-regulated genes but not in liver FDR = 0.074 for up-regulated genes; FDR = 0.248 for down-regulated genes.

ConclusionMiR-125a is over-expressed in liver in hyperglycaemic GK rats relative to normoglycaemic BN rats, and our array data also suggest miR-125a is over-expressed in adipose tissue. We demonstrate the use of in-silico tools to provide the basis for further investigation of the potential role of miR-125a in T2D. In particular, the enrichment of predicted miR-125a target genes among differentially expressed genes has identified likely target genes and indicates that integrating global miRNA and mRNA expression data may give further insights into miRNA-mediated regulation of gene expression.

Electronic supplementary materialThe online version of this article doi:10.1186-1755-8794-2-54 contains supplementary material, which is available to authorized users.

Blanca M Herrera, Helen E Lockstone contributed equally to this work.

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Autor: Blanca M Herrera - Helen E Lockstone - Jennifer M Taylor - Quin F Wills - Pamela J Kaisaki - Amy Barrett - Carme Camps

Fuente: https://link.springer.com/



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