The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer

Guzman J, Hart M, Weigelt K, Neumann AD, Aigner A, Andolfi C, Handle F, Rheinheimer S, Fischer U, Immel UD, Lieb V, Meese E, Culig Z, Wullich B, Taubert H, Wach S (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 15

Article Number: 10272

Journal Issue: 1

DOI: 10.1038/s41598-025-95250-0

Abstract

Prostate cancer that is resistant to anti-androgen treatment, such as enzalutamide, represents a therapeutic challenge. To study their molecular and functional features, the enzalutamide-resistant PCa cell lines LNCaP Abl EnzR and DuCaP EnzR constitute valuable in vitro models. In this work, we explored two different strategies for reducing AR/AR-V7/c-Myc. MED12 knockdown decreased the protein expression of AR, AR-V7 and c-Myc. Similarly, we identified AR and AR-V7 as targets of miR-454-3p. Concomitantly, the transfection of synthetic miR-454-3p reduced the protein expression of AR in both EnzR cell lines and that of c-Myc and AR-V7 in the DuCaP EnzR cell line without affecting MED12. Despite these similar molecular effects, differences were observed at the cellular level, with siMED12, but not miR-454, reducing cell viability, and no additive effects upon double treatment were observed. Taken together, the results of our study suggest MED12 as a potential target for future PCa treatment in conjunction with enzalutamide resistance. Furthermore, miR-454-3p, which directly targets AR and AR-V7 and indirectly influences c-Myc protein expression, reveals new molecular mechanisms in PCa biology.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universität Leipzig Germany (DE) Medizinische Universität Innsbruck Austria (AT) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE)

How to cite

APA:

Guzman, J., Hart, M., Weigelt, K., Neumann, A.-D., Aigner, A., Andolfi, C.,... Wach, S. (2025). The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-95250-0

MLA:

Guzman, Juan, et al. "The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer." Scientific Reports 15.1 (2025).

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