In vivo study of co-activators and co-repressors of androgen receptor in Prostate Câncer

• Grant number: 19/00156-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2019
• End date: July 31, 2023
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Sabrina Thalita dos Reis Faria
• Grantee: Ruan César Aparecido Pimenta
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Prostate Cancer (PCa) is characterized by slow growth and represents a type of androgen dependent neoplasia. The Androgen Receptor (AR) plays a key ro le in prostate carcinogenesis and metastasis. Thus, Androgen Deprivation Therapies (ADT) are often used to treat PCa. However, at the time when PCa acquired castration-resistant phenotype (CPRC), ADT is no longer effective. In fact, it is now known that androgenic signaling persists even after the transition from the CaP hormone sensitive (HSPC) to CRPC. Among other factors that contribute to a clinical worsening of these patients are the lipid profiles, where it fits cholesterol, also known to be a common side effect ADT of for CRPC. In this sense, we emphasize the AR cofactors, which can recruit numerous transcriptional enzyme cofactors, such as p160 (SRC-1, SRC-2 and SRC-3), Histone Acetyltransferase (p300 and CBP), and corepressors, Cytoskeleton Protein (ARA67), Nuclear Receptor (SMRT/NCoR2) and IL-6. We also highlight the action of the microRNAs, 137 and 17-5p, which targets the p160 families and the CBP/p300 complex, respectively, which are also promising molecules in this sense. Thus, we believe that the joint study of these molecules in an in vivo model of hypercholesterolemic CPRC can elucidate the transactivation of the RA axis in this pathology, thus identifying possible biomarkers with potential therapeutic target. (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)

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., 2023-06-01. (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., 2023-07-13. (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)

PIMENTA, Ruan César Aparecido. Cholesterol-driven enhancement of the androgenic axis and the suppressive role of miR-137 in p160 coactivators on prostate cancer. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.