Validation and functional studies of differentially expressed miRNAs in high grade serous carcinoma of patients with different clinical developments

• Grant number: 16/09349-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 15, 2016
• End date: August 30, 2017
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Rafael Malagoli Rocha
• Grantee: Nayra Soares Do Amaral
• Supervisor: George A. Calin
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Institution abroad: University of Texas MD Anderson Cancer Center (MD Anderson), United States
• Associated to the scholarship: 14/03021-1 - Identification of microRNAs differentially expressed in serous carcinomas of high-grade patients with different clinical outcomes, BP.DR

Abstract

Despite the high mortality of ovarian cancer, yet little is known about markers that can help early diagnosis and prediction of therapeutic response of women with high grade serous adenocarcinoma. Some studies have demonstrated the role of miRNAs in the progression of ovarian cancer, the prognosis and the resistance to drugs. In our study we have selected homogeneous samples concerning the histological type, surgery and clinical staging, with the aim of evaluating the expression of miRNAs in patients with different clinical developments. We have identified 53 hipoexpressos miRNAs in the Group of non-sensitive in comparison to sensitive patients to chemotherapy. Among the 53 differentially expressed miRNAs, we observe that the hsa-miR-616-3 p, hsa-miR-4267, hsa-miR-4448, hsa-miR-934 and hsa-miR-155-5 p were associated with disease-specific survival and relapse-free survival e, however little is known about the function and what the targets of these miRNAs. Objectives: This project seeks to validate and elucidation of the mechanisms and targets of differentially expressed miRNAs identified between patients with ovarian serous adenocarcinoma, sensitive and non-sensitive to chemotherapy associated with survival. Method: The miRNAs will be validated by ISH and real-time PCR, the targets of miRNAs are validated for Luciferase assay and Immunohistochemistry. Functional tests will be made by transfection of mimetic miRNA in an ovarian cell line, assessing its impact in migration testing, proliferation and apoptosis. (AU)

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)

FUENTES-MATTEI, ENRIQUE; BAYRAKTAR, RECEP; MANSHOURI, TAGHI; SILVA, ANDREIA M.; IVAN, CRISTINA; GULEI, DIANA; FABRIS, LINDA; DO AMARAL, NAYRA SOARES; MUR, PILAR; PEREZ, CRISTINA; et al. miR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2. JCI INSIGHT, v. 5, n. 1, JAN 16 2020. (16/09349-4)