Integrative analysis of miRNAs-mRNAs expression from a DNA microarray database: influence of Pregnenolone on lipoprotein activities

• Grant number: 19/03503-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2019
• Effective date (End): June 30, 2020
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Mario Hiroyuki Hirata
• Grantee: Vanessa Barbosa Malaquias
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The miRNAs play an important role in the downregulation of mRNA expression at the post-transcriptional level. Bioinformatics tools are useful for elucidating the molecular mechanisms associated with interactions between miRNAs- mRNAs target through transcriptional regulatory networks. In the present study, an integrative analysis will be performed based on expression profiles of miRNAs and target mRNAs obtained from public databases to understand the possible contribution of pregnenolone in the molecular mechanisms involved in the decrease of plasma cholesterol. The public mRNA data set (GSE13688) obtained from Gene Expression Omnibus 2R (GEO2R), provides mRNAs differentially expressed between normocaloric and hypercaloric diets with or without administration of Pregnenolone 16 alpha-carbonitrile, in Mus Musculus mouse species. The regulatory miRNAs of the selected target mRNAs will be identified through the TargetScanMouse 7.2 and miRTarBase data platform. The mRNAs related to cholesterol homeostasis will be analyzed by Ingenuity Pathway Analyzes (IPA) software integrating with miRNA targets and potential metabolic pathways. The results are expected to contribute to understanding the regulatory mechanisms of pregnenolone in genes related to metabolic pathways of cholesterol, as well as to propose potential biomarkers providing subsidy for future in vitro and in vivo studies.