The role of tumor suppressor miRNA-206 and your targets predict in the ventral prostate of rats submitted of maternal protein restriction: functional studies in prostatic cell

Abstract

The DOHaD (Developmental Origin of Health and Disease) approach seeks to establish the correlation between the incidence of diseases in adulthood and aging in the consequence of events suffered during the beginning of development. One of its most used models for DOHaD studies is the submission of rodents to maternal protein restriction (MPR). Experimental studies have already shown that it is responsible for inhibiting normal prostate development and increasing the incidence of Prostate Cancer (PCa) with aging. One of the main consequences of these events is the epigenetic changes that accompany the offspring throughout life as changes in non-coding RNAs, such as miRNAs. Recently, our research group has been studying globally the molecular and epigenetic mechanisms of alterations in the prostate of animals submitted to RPM. Thus, the objective of this work will be to analyze the role of tumor suppressor miR-206 (selected from bioinformatics analysis) in the ventral prostate (VP) of animals on a postnatal day (DPN) 21 that underwent RPM. For this, we will use data from the PV miRNA sequencing of Sprague Dawley rats that were divided into two experimental groups: CTR group (control, with 17% protein diet, n = 6) and GLLP (protein restriction during pregnancy and lactation, 6% diet, n = 6), and that were euthanized in the DPN 21. These data are part of the database of our research group (generated in the FAPESP 2017 / 01063-7 process). From the miRNA sequencing data, we identified the differentially expressed (DE) targets and selected the miR206 to be validated. Validations will take place using RT-qPCR in the animals VP. In addition, we will also carry out functional assays that mimic the expression of miRNA-206 in prostate cells, as well as viability and cell migration assays. With this work, we hope to identify the role of miR206 in the PV of animals submitted to RPM and its functional role for prostate cells (PNT2).(AU)