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Evaluation of the role of microRNAs -17-5p and -137 on androgen receptor cofactors in castration-resistant prostate cancer: in vitro and in vivo study in a hypercholesterolemic model

Abstract

Castration-resistant metastatic prostate cancer (CRPC) is an incurable disease, a large number of studies have been looking for therapeutic alternatives based on the molecular pathways that act in this phase of the neoplasia. Alterations in the androgen receptor occur frequently in the progression of this neoplasia and the androgen receptor cofactors appear as attractive molecules, since these cofactors also play an important role in lipogenesis, metabolism, proliferation, apoptosis and cell cycle. It is believed that microRNAs may be involved in regulating the expression of these cofactors. Present study will seek to establish a hypercholesterolemia in vivo model in NOD.CB17-SCID mice with CPRC, where will be evaluated the expression profile of genes and proteins co-activating of the androgen receptor, p160 (SRC-1, SRC-2 and SRC-3), Histone Acetyl-transferase (p300 and CBP) and IL-6 and of its co-repressors such as Cytoskeletal Protein (ARA67) and Nuclear Receiver (SMRT/NCoR2). In this model, will be evaluated the effect of the administration of miR-137 and miR-17-5p in addition to the lipid profile of the animals and the administration of these same microRNAs will be evaluated in Prostate Cancer cell line (PC3). (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; 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)
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)

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