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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.<\/jats:p>","DOI":"10.1038\/s41598-025-95250-0","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:53:03Z","timestamp":1742950383000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer"],"prefix":"10.1038","volume":"15","author":[{"given":"Juan","family":"Guzman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Weigelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Aigner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Andolfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Handle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Rheinheimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta D.","family":"Immel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Lieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckart","family":"Meese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Culig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Wullich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helge","family":"Taubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Wach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"95250_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray, F. et al. 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