Global profiling of non-coding RNA alterations in the ventral prostate of young rats subjected to a perinatal maternal protein restriction

Abstract

In the last decades, it has been observed an increase in the incidence of metabolic disorders, such as obesity, diabetes and even some types of cancer. Epidemiological evidences show that these diseases can originate from insults suffered by individuals during the intrauterine life, a condition known as Fetal Programming (FP). The perinatal period is characterized by high plasticity and the ability of the embryo/fetus to adapt to environmental changes by altering gene expression through epigenetic mechanisms. Recently, our group demonstrated that maternal protein restriction promotes prostate carcinogenesis in older offspring rats; however, the molecular mechanisms involved in this process remain unexplored. The advent of next-generation sequencing has revealed the importance of the non-coding transcriptome in the modulation of cellular processes. Thus, we aim to identify the global profile of small non-coding RNAs (microRNAs, piwi-interacting RNAs) deregulation in prostate samples of offspring rats subjected to a maternal low protein diet during the perinatal period. In this study, male Sprague Dawley rats born to dams fed with a standard diet (17% protein) or a low protein diet (6% protein) during gestation and lactation were euthanized on postnatal day 21 and (concluded step in Brazil), the ventral prostate was processed for small RNA-sequencing, using the HiSeq-2500 Illumina platform (concluded step in South Korea). During the 6 months internship, we will compare our microRNome data to the human prostatic adenocarcinoma data available in the "The Cancer Genome Atlas" database (TCGA), in order to find potential molecular pathways deregulated in the prostate of restricted offspring that could be related to the development of prostatic lesions in older animals. In-silico analyses will be performed to predict mRNA targets of the altered microRNAs, followed by the construction of regulatory networks and ontological pathways. These data will be used for target validation by RT-qPCR, western blotting and functional analysis when the Candidate returns to Brazil. Thus, we expect not only to improve the current knowledge on how prostate development is affected by maternal low protein diet exposure, but also identify common potential signaling pathways between the development of rat and human prostate carcinogenesis. The internship at Dr. Lam's Laboratory will provide the PhD Candidate Flávia Bessi Constantino with experience in bioinformatics, particularly on basic programming skills, as well as the processing and analysis of big data. These skills will be useful for the advancement of her PhD. research when she returns to Brazil. (AU)