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Genomic edition with CRISPR/Cas9 to evaluate the role of MMP9 and the regulator miR21 in Prostate Cancer

Grant number: 18/19906-3
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2019
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Sabrina Thalita dos Reis Faria
Grantee:Juliana Alves de Camargo
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Prostate Cancer (PC) corresponds to 10% of all cancers, being considered the sixth common neoplasm in the world. The high prevalence represents a major health problem, with a strong economic impact, the screening, the diagnosis, the treatment and the disease. The treatments are done according to the patient diagnosis. In high-risk and metastatic cases, it is a systemic treatment through surgical or drug castration. However, treatment in about 80% of patients with metastatic tumor does not present efficiency. The response to this resistance of tumor cells, can be caused by genetic alterations, generating mutations, chromosomal alterations and also related to gene expression. MicroRNAs play an important role in the regulation of oncogenes, such as miR-21, which acts on the RECK tumor suppressor gene and MMP-9 oncogene, acting in the process of migration and invasion of tumor cells into other tissues, generating metastasis.Due to the importance of these genes in carcinogenesis, further investigations are needed regarding their role in CP, these investigations are based on the silencing of these molecules to better evaluate their role. To date the studies are performed with RNAi and ASO, however, these techniques have limitations, by only silencing, reducing gene expression, but not blocking them completely. With the CRISPR-Cas9 technique, from the prokaryote invader resistance system adapted for eukaryotes, it is possible to edit the genome and complete blocking of these markers, which allows a better study of them in several pathologies, especially for the cancer. Thus, we believe that are extremely important to study the molecular markers miR-21 and MMP-9 in metastatic Prostate Cancer using this new methodology. (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)
PIMENTA, RUAN; MIOSHI, CAROLINA MIE; GONCALVES, GUILHERME L.; CANDIDO, PATRICIA; CAMARGO, JULIANA A.; GUIMARAES, VANESSA R.; CHIOVATTO, CAROLINE; GHAZARIAN, VITORIA; ROMAO, POLIANA; DA SILVA, KARINA SERAFIM; et al. Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 11, p. 16-pg., . (18/26528-5, 18/19906-3, 19/19138-9, 22/09284-0, 19/00156-7, 21/02341-6, 20/01317-1)
PIMENTA, RUAN; CAMARGO, JULIANA A.; GONCALVES, GUILHERME L.; GHAZARIAN, VITORIA; CANDIDO, PATRICIA; GUIMARAES, VANESSA R.; ROMAO, POLIANA; CHIOVATTO, CAROLINE; DA SILVA, KARINA SERAFIM; DOS SANTOS, GABRIEL A.; et al. Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model. MOLECULAR BIOLOGY REPORTS, v. 50, n. 9, p. 13-pg., . (18/26528-5, 18/19906-3, 19/19138-9, 22/09284-0, 19/00156-7, 21/02341-6, 20/01317-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAMARGO, Juliana Alves de. CRISPR/Cas9 genomic editing to evaluate the role of MMP9 and microRNA-21 in metastatic prostate cancer: In vitro and in vivo study. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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