Global profile of expression of MicroRNAs in the ventral prostate of rats subjected to maternal protein restriction: Perinatal effects and reflexes in aging

Author(s)

Flávia Bessi Constantino

• Document type: Doctoral Thesis
• Press: Botucatu. 2021-06-17.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2021-05-21
• Advisor: Luis Antonio Justulin

Abstract

In the last decades, there has been an increase in the incidence of cancer in the population. Studies show that cancer can originate through insults suffered by individuals during intrauterine life, a condition known as Fetal Programming. (PF). The perinatal period is characterized by the ability of the embryo / fetus to adapt to environmental changes, altering gene expression by post-transcriptional mechanisms. Recently, we demonstrated that maternal protein restriction promotes prostate carcinogenesis in elderly rats; However, information about the molecular mechanism involved in this process is lacking. Thus, we aimed at identifying possible deregulated microRNAs in young programmed rats and locate their possible targets associated with prostate carcinogenesis. For this, male Sprague Dawley rats born to mothers fed a standard diet (17% protein) - a control group (CTR) or a low protein diet (6% protein) - a gestational and lactational low protein diet (GLLP), during pregnancy and lactation were sacrificed on the postnatal day 21. We observed a delay in the development of the ventral prostate and increased levels of testosterone and estrogen expression in GLLP rats. In addition, 20 miRNAs were identified as differentially expressed, 6 downregulated and 14 upregulated. The enrichment results for downregulated miRNAs are related to cancer and angiogenesis pathways, while upregulated miRNAs are enriching endoplasmic reticulum and carcinoma pathways. The reanalysis of miRNA sequencing from TCGA revealed 7 in common with the GLLP group. One of them is miR-33 which, in addition to being down regulated in the prostate, is also unregulated in the testis, adrenal gland and liver. Their overexpression in transfected cells caused a decrease in cell viability and your target, CYP1B1, which is an important enzyme in estrogen metabolism, leading to carcinogenesis mediated by changes in hormone levels. We concluded that miR-33 is an important target to explain the changes caused by maternal LPD and can also be considered the biomarker because it is unregulated in several organs. (AU)

• FAPESP's process: 17/08716-6 - Global methylation and microRNAs expression in ventral prostate of rats offspring submitted to maternal protein restriction: perinatal effects and reflexes on aging
• Grantee: Flávia Bessi Constantino
• Support Opportunities: Scholarships in Brazil - Doctorate