Genomic edition with CRISPR / Cas9 to evaluate the role of MMP9 and it regulator MIR21 in prostate cancer

• Grant number: 17/17362-3
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2018
• End date: February 28, 2021
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Sabrina Thalita dos Reis Faria
• Grantee: Sabrina Thalita dos Reis Faria
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ericka Barbosa Trarbach ; Fabio Pescarmona Gallucci ; Juliana Alves de Camargo ; Kátia Ramos Moreira Leite ; Miguel Srougi ; Nayara Izabel Viana ; Ruan César Aparecido Pimenta ; William Carlos Nahas

Abstract

Prostate cancer (PC) corresponds to about 10% of all cancers, being considered the sixth most common neoplasm in the world. Due to its high prevalence, it represents an important health problem, with a strong economic impact if we consider the tracing, diagnosis, treatment and mortality due to the disease. The treatments are done according to the patient's diagnosis. In cases of high risk and metastatic, it is considered a systemic treatment through surgical or drug castration. However, this treatment in approximately 80% of the patients with the metastatic tumor is not effective. The response to this resistance of tumor cells may be the genetic changes, which generate mutations, chromosomal changes and also alterations in 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 the MMP-9 oncogene, both of which act in the process of migration and invasion of tumor cells into other tissues. metastases. 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 the blocking of these markers, which allows a better study of them in several pathologies, especially for the cancer. Thus, we believe that it is extremely important to study the molecular markers miR-21 and MMP-9 in metastatic prostate cancer using this new methodology. (AU)