Integrative analysis of the multi-omic profile of the prostate of rats subjected to maternal protein restriction: identification of potential biomarkers of the developmental origin of prostate cancer (PCa)

• Grant number: 23/17519-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 01, 2024
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Luiz Marcos Frediani Portela
• Supervisor: Joao Pedro de Magalhaes
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: University of Birmingham, England
• Associated to the scholarship: 21/00340-2 - Global expression profile of long non-coding RNAs (lncRNAs) in the ventral prostate of rats submitted to Maternal Protein Restriction: Characterization and functional validation, BP.DR

Abstract

The concept of Developmental Origin of Health and Disease (DOHaD) seeks to establish the correlation of diseases in adult life with events occurring during intrauterine development and/or early childhood. One of the models used for DOHaD studies is the submission of rodents to maternal protein restriction (MPR). MPR is responsible for the delay in the normal development of the prostate, in addition to increasing the incidence of Prostate Cancer (CaP) as the offspring ages. One of the main consequences of DOHaD is the epigenetic changes that accompany the offspring throughout life. In recent years, long non-coding RNAs (lncRNAs) have been gaining prominence since they epigenetic control. In this context, our research group has been dedicated to comprehensively understanding the molecular mechanisms in the Developmental origins of PCs using omics data, however, the elucidation of the role of lncRNA in these prostate changes has not yet been established. Thus, the objective of this work will be to analyze the global profile of lncRNA expression in the ventral prostate (VP) of the offspring of rats submitted to MPR and trace an interaction network between lncRNA to the proteomic, transcritome profile. For that, male offspring rats (21 and 540 days old) born from dams fed a standard diet (17% protein) or with a low protein diet (6% protein) during gestation and lactation will be used. After this period, the animals will be euthanized, and the VP will be collected. The transcriptome, small RNA sequence, and proteomic profile were generated (FAPESP Proc. 2017/0163-7). After this, we will perform a comparative analysis of these data with databases between the experimental groups. These results will be subjected to integrative analysis using lncRNAs as a central epigenetic regulator, generating interaction networks between lncRNAs-mRNAs/miRNAs/proteins. This application for a fellowship is linked to a regular FAPESP grant (Proc. 2022/03390-0) which aims to investigate, through global analyses, possible altered molecular mechanisms in the offspring rats at 21 days old and that could lead to the higher incidence of lesions observed in these rats with aging. With the development of these projects, our group will obtain robust data on a large scale, not only from altered molecular pathways during the early stages of development but also from the late repercussions of this fetal programming model.