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Analysis of the miRNAs involved in the regulation of MMP2 and MMP9 and regulators, and the implication of this adjustment in cell invasion in prostate adenocarcinoma process: in vivo and in vitro studies

Grant number: 15/00845-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2015
Effective date (End): June 05, 2018
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Sabrina Thalita dos Reis Faria
Grantee:Renato Fidelis Ivanovic
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Prostate Cancer (PCa) is the most common in men. 70mil in 2014 new cases are expected; a reflection of the higher life expectancy and frequent diagnoses. Nevertheless, it is responsible for only 6% of cancer deaths, and almost 80% survival. These ambiguities reflect the heterogeneity of the disease. The discovery and use of tumor markers are positively influencind the early detection, diagnosis and staging of a number of malignancies. Among the promising molecular markers are the genes belonging to the family of matrix metalloproteinase (MMP). MMPs degrade components of the extracellular matrix (ECM), increasing tumor invasion. Its activity is mainly regulated by inhibitors of metalloproteinases (TIMP). However, in recent years several studies have been published involving the gene expression of MMPs and their regulators in various neoplasms. The conflicting results of these indicate that there may be other mechanisms involved in the regulation not only of MMPs but also in genes that regulate, such as microRNAs (miRNA). MiRNAs act at the post-transcriptional regulation of gene expression by binding to the messenger RNA (mRNA), affecting protein expression. A single miRNA can regulate many mRNA, making their study a broad field science. Some microRNAs have been demonstrated as regulators of MMPs, TIMPs as well, have not yet been described miRNAs regulating its expression. Previously, our group identified changes in the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, RECK and demonstrated an association with protein expression and prognostic factors of PCa (ST Reis, 2012). Knowing the importance of these genes in carcinogenesis of the prostate cancer, we decided to evaluate the role of microRNAs (21, 338-3p, 221, 222, 618, 29b) in the regulation of these genes and the involvement in regulation of cell invasion in cell lines and in in vivo experimental model of PCa. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
IVANOVIC, RENATO F.; VIANA, NAYARA I.; MORAIS, DENIS R.; MOURA, CAIO; SILVA, IRAN A.; LEITE, KATIA R.; PONTES-JUNIOR, JOSE; NAHAS, WILLIAM C.; SROUGI, MIGUEL; REIS, SABRINA T.. miR-618: possible control over TIMP-1 and its expression in localized prostate cancer. BMC CANCER, v. 18, . (15/00845-6, 12/21833-8)
IVANOVIC, RENATO F.; VIANA, NAYARA I.; MORAIS, DENIS R.; SILVA, IRAN A.; LEITE, KATIA R.; PONTES-JUNIOR, JOSE; INOUE, GUSTAVO; NAHAS, WILLIAM C.; SROUGI, MIGUEL; REIS, SABRINA T.. miR-29b enhances prostate cancer cell invasion independently of MMP-2 expression. CANCER CELL INTERNATIONAL, v. 18, . (12/21833-8, 15/00845-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
IVANOVIC, Renato Fidelis. Analysis of miRNAs involved in the regulation of MMP9 and its consequences to cell invasion of prostate cancer: in vivo and in vitro study. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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