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Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model

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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. ; Silva, Iran A. ; Nahas, William C. ; Leite, Katia R. ; Pessoa, Ana Flavia Marcal ; Viana, Nayara I. ; Reis, Sabrina T.
Total Authors: 16
Document type: Journal article
Source: MOLECULAR BIOLOGY REPORTS; v. 50, n. 9, p. 13-pg., 2023-07-13.
Abstract

BackgroundPreviously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia.Methods and resultsIn vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 & mu;g/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation.ConclusionOur results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6. (AU)

FAPESP's process: 18/26528-5 - Adaptive mechanisms of renal function in a model of adriamycin-induced nephrotoxicity: participation of sirtuin 1 and claudin-1
Grantee:Guilherme Lopes Gonçalves
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/19906-3 - Genomic edition with CRISPR/Cas9 to evaluate the role of MMP9 and the regulator miR21 in Prostate Cancer
Grantee:Juliana Alves de Camargo
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 19/19138-9 - Study of the effect of miR-137 on cell line of castration resistant prostate cancer in a hypercholesterolemic environment
Grantee:Vitória Ghazarian Nunes
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 22/09284-0 - Searching for alterations in the expression of mismatch-type repair proteins (MLH1, MSH2, MSH6, and PMS2) in Prostate Cancer
Grantee:Karina Serafim da Silva
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 19/00156-7 - In vivo study of co-activators and co-repressors of androgen receptor in Prostate Câncer
Grantee:Ruan César Aparecido Pimenta
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 21/02341-6 - Establishment of the animal model of Peyronie's disease fibrin-induced
Grantee:Caroline Brandão Chiovatto
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 20/01317-1 - 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
Grantee:Sabrina Thalita dos Reis Faria
Support Opportunities: Regular Research Grants