Maternal protein restriction and prostate carcinogenesis: integrative approaches based on omics analysis

Abstract

In the last decades, an increase in diseases incidence related to alterations in the metabolism that affect both children and adults. Among the most prevalent are Obesity, Diabetes, cardiovascular disease and even some kinds of Cancer. Epidemiological evidence shows that chronic diseases may originate from even insults suffered during intrauterine development, a condition known as Fetal Programing (FP). However, the molecular mechanisms involved in this process are poorly understood. In this context, the increase of large-scale sequencing technologies based on the combination of "omes" (transcriptome, MicroRNAome, proteome) using bioinformatics tools has enabled a global integrative view of molecular mechanisms in normal and pathological conditions. Considering results from our group that demonstrate the role of maternal protein restriction in altering development and increasing the incidence of prostatic lesions in offspring of rats, the aim of this work will be to integrate the global expression profiles of microRNAs, gene expression transcriptome and protein of prostate from rats that have undergone maternal protein restriction to identify molecular pathways involved in the development of prostatic lesions. For this, male Sprague Dawley rats with 540 days born from mothers fed standard chow (17% protein) or with hypoprotein chow (6% protein) during gestation and lactation will be used. After this period, the animals will be euthanized, and the ventral prostate will be collected. The global profiles of expression of microRNAs and mRNAs for next-generation sequencing (HigSeq-2000 Illumina), and proteins (proteome), by mass spectrometry (LC-Ms/Ms) will be analyzed. After this, an integrative and comparative analysis of these data will be performed between the experimental groups. These results will be compared to data from global mRNA, global microRNA and global protein for prostatic adenocarcinoma, available in the literature (databases). This application for a postdoctoral fellowship is linked to a regular FAPESP grant (Proc. 2017/01063-7) which aims to investigate, through global analyzes, possible altered molecular mechanisms in the offspring of restricted rats at 21 days of age 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 on rat prostate. (AU)