Analyses of the regulatory transcriptional mechanisms mediated by miRNAs in metabolic syndrome

Abstract

Metabolic Syndrome (MS) is a group of pathologies (diabetes, dyslipidemia, hypertriglyceridemia, hypertension and obesity) associated to higher risk of mortality, cardiovascular events and high medical costs. MicroRNAs (miRNAs) are small noncoding RNA molecules with extensive gene regulatory activity. MiRNAs are involved in the pathophysiology of several metabolic diseases and, therefore, are potential biomarkers. The aim of this research is to use systems biology approaches to study potential regulatory roles of miRNAs in MS. Publicly available gene expression microarray data will be used to build gene networks and modules consistently associated with MS. These data will be integrated with protein-protein interaction data and miRNAs gene target data to identify miRNAs that influence molecular pathways specifically associated with MS. Our results will be then compared with miRNA expression profile data of patients diagnosed with MS. These data will be generated by high throughput sequencing technology (miRNA-seq) and its technical validation will be performed by qPCR. In addition, functional validation of miRNAs will be performed in cells co-transfected with the miRNA and the reporter vector containing the miRNA target gene. Thus, the identification of miRNAs and gene networks associated to different metabolic pathologies will improve our understanding about the complex molecular and pathophysiological mechanisms of the metabolic syndrome. (AU)