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Global expression profile of lncRNAs in the ventral prostate of offspring rats submitted to maternal low protein diet: a DOHaD approach

Abstract

The concept of the Developmental Origin of Health and Disease (DOHaD) seeks to establish correlations between exposure to adverse conditions in early life and the development of disease in adulthood. Epidemiological and experimental studies have shown that some types of cancer can originate early in life, including prostate cancer (PCa). Although the mechanisms involved in the developmental origin of PCa are not fully known, changes in epigenetic markers have been identified as potential agents involved in this process. Long non-coding RNAs (lncRNAs) constitute a class of RNAs still poorly characterized, with the potential to participate in epigenetic reprogramming, impacting normal development and pathophysiology prostatic. Thus, the aims of this work will be to characterize the global expression profile of lncRNAs, as well as to identify their networks of interactions with miRNA/mRNA/proteins in the ventral prostate (VP) of the offspring of Sprague Dawley rats submitted to maternal protein restriction (MPR). These data may be correlated to the developmental delay and prostatic carcinogenesis, observed in the histological analysis of these animals. For this, data from RNA-Seq (GSE180673), small non-coding RNAs (GSE180674), and the proteomic profile (SANTOS et al, 2020) of animals submitted to RPM (6% proteins x 17% of the group of control) and euthanized on postnatal days (PND) 21 and 540. From the RNA-Seq data, the lncRNAs expressed in the VP of rats will be identified and characterized, as well as the lncRNAs differentially expressed (DE) in each age. These results will be compared with data obtained from patients with PCa. Integrative analyzes will also be performed in silico for the prediction of molecular networks lncRNAs-miRNA/mRNA/proteins deregulated by RPM in the PV of these animals. lncRNAs will be selected for validation in the VP of mice in the different experimental groups, by means of RT-qPCR, and functional assays with inhibition of the expression of selected lncRNAs in prostate human cells (benign and tumor) will also be performed. Thus, we hope to identify epigenetic mechanisms related to the expression of lncRNAs and their interaction networks involved in developmental alterations and prostatic carcinogenesis in rats submitted to RPM. (AU)

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