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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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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 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 results

In 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 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 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.

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Data Availability

The datasets used and/or analyzed during the current study are available to the corresponding author upon reasonable request.

Code Availability

Not Applicable.

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Acknowledgements

We thank Prof Dr Edna Frasson de Souza Montero for making the Bioterium of the Anesthesiology Laboratory of the Hospital das Clínicas of the Faculty of Medicine (LIM08) available for carrying out the in vivo experiments and/also to Mr. Mario Matsuo Itinoshe for the support with the animals. To the Laboratório de Investigação Médica da disciplina de Urologia (LIM55).

Funding

This work was supported by grants from the São Paulo Research Foundation (FAPESP) to Ruan Pimenta (2019/00156-7), Vitória Ghazarian (2019/19138-9), Juliana Alves de Camargo (2018/19906-3), Guilherme Lopes Gonçalves (2018/26528-5), Caroline Chiovatto (2021/02341-6), Karina Serafim (2022/09284-0) and Sabrina T. Reis (2020/01317-1).

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Authors and Affiliations

  1. Laboratorio de Investigação Médica 55 (LIM55), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo 455, 2° floor, room 2145, Sao Paulo, Sao Paulo, SP, BR, SP, 01246- 903, Brazil

    Ruan Pimenta, Juliana A. Camargo, Vitória Ghazarian, Patrícia Candido, Vanessa R. Guimarães, Poliana Romão, Caroline Chiovatto, Karina Serafim da Silva, Gabriel A. dos Santos, Iran A. Silva, Kátia R. Leite, Nayara I. Viana & Sabrina T. Reis

  2. D’Or Institute for Research and Education (IDOR), Sao Paulo, Brazil

    Ruan Pimenta & Gabriel A. dos Santos

  3. Laboratory of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil

    Guilherme L. Gonçalves

  4. Uro-Oncology Group, Urology Department, University of Sao Paulo Medical School and Institute of Cancer Estate of Sao Paulo (ICESP), Sao Paulo, SP, 01246-000, Brazil

    William C. Nahas

  5. Natural Products and Derivatives Laboratory, Department of Surgery, University of São Paulo Medical School, São Paulo, SP, 01246-903, Brazil

    Ana Flávia Marçal Pessoa

  6. Centro Universitário São Camilo, São Paulo, 04263-200, Brazil

    Caroline Chiovatto & Karina Serafim da Silva

  7. Universidade do Estado de Minas Gerais - UEMG, Avenida Juca Stockler, Passos, MG, 1130, Brasil

    Nayara I. Viana

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  1. Ruan Pimenta
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Contributions

All authors discussed the results, revised the manuscript draft, and contributed: Ruan Pimenta wrote the manuscript and performed the in vitro and in vivo experiments, to the study design, intellectual input, to statistical analysis assisted in drafting and critical reading. Juliana A. Camargo contributed to in vitro and in vivo experiments. Guilherme L. Gonçalves contributed to in vivo experiments. Vitória Ghazarian performed the in vitro experiments. Patricia Candido contributed to the study design and performed the in vitro experiments. Vanessa R. Guimarães contributed to in vitro experiments. Poliana Romão contributed to in vitro experiments. Caroline Chiovatto contributed to in vivo experiments. Karina Silva contributed to in vivo experiments. Gabriel A dos Santos contributed to in vitro experiments. Iran A Silva contributed to intellectual input. Miguel Srougi supervised the experiments and intellectual information. William C. Nahas supervised the experiments and intellectual input. Kátia R. Leite supervised the experiments, contributed to the study design and intellectual input. Ana Flávia M. Pessoa contributed to intellectual input and in vivo experiments Nayara I. Viana supervised the experiments, contributed to the study design, intellectual input. Sabrina T. Reis contributed to the study design, supervised the experiments, intellectual input, to statistical analysis assisted in drafting and critical reading and funding action.

Corresponding author

Correspondence to Ruan Pimenta.

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This study was submitted and approved by the Research Ethics Committee of the University of Sao Paulo Medical School under the number #1360/2019.

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Pimenta, R., Camargo, J.A., Gonçalves, G.L. et al. Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model. Mol Biol Rep 50, 7333–7345 (2023). https://doi.org/10.1007/s11033-023-08638-4

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