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

Abstract

Background Previously, 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 inflamma tion 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 results In vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expres sion, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 µg/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. Conclusion Our results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory media tor expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflamma tory mediators p300, PCAF, and IL-6.