Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p

Abstract Understanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into pros...

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Autores principales:	Roberto H. Barbier, Edel M. McCrea, Kristi Y. Lee, Jonathan D. Strope, Emily N. Risdon, Douglas K. Price, Cindy H. Chau, William D. Figg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e06fd1fa19174341a92b77d01fce5e9c
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spelling	oai:doaj.org-article:e06fd1fa19174341a92b77d01fce5e9c2021-12-02T16:53:01ZAbiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p10.1038/s41598-021-90143-42045-2322https://doaj.org/article/e06fd1fa19174341a92b77d01fce5e9c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90143-4https://doaj.org/toc/2045-2322Abstract Understanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into prostate cancer cells. In this study we observed and investigated the mechanism of induction of SLCO1B3 by abiraterone. Prostate cancer cells (22Rv1, LNCaP, and VCAP) were treated with anti-androgens and assessed for SLCO1B3 expression by qPCR analysis. Abiraterone treatment increased SLCO1B3 expression in 22Rv1 cells in vitro and in the 22Rv1 xenograft model in vivo. MicroRNA profiling of abiraterone-treated 22Rv1 cells was performed using a NanoString nCounter miRNA panel followed by miRNA target prediction. TargetScan and miRanda prediction tools identified hsa-miR-579-3p as binding to the 3′-untranslated region (3′UTR) of the SLCO1B3. Using dual luciferase reporter assays, we verified that hsa-miR-579-3p indeed binds to the SLCO1B3 3′UTR and significantly inhibited SLCO1B3 reporter activity. Treatment with abiraterone significantly downregulated hsa-miR-579-3p, indicating its potential role in upregulating SLCO1B3 expression. In this study, we demonstrated a novel miRNA-mediated mechanism of abiraterone-induced SLCO1B3 expression, a transporter that is also responsible for driving androgen deprivation therapy resistance. Understanding mechanisms of abiraterone resistance mediated via differential miRNA expression will assist in the identification of potential miRNA biomarkers of treatment resistance and the development of future therapeutics.Roberto H. BarbierEdel M. McCreaKristi Y. LeeJonathan D. StropeEmily N. RisdonDouglas K. PriceCindy H. ChauWilliam D. FiggNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roberto H. Barbier Edel M. McCrea Kristi Y. Lee Jonathan D. Strope Emily N. Risdon Douglas K. Price Cindy H. Chau William D. Figg Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
description	Abstract Understanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into prostate cancer cells. In this study we observed and investigated the mechanism of induction of SLCO1B3 by abiraterone. Prostate cancer cells (22Rv1, LNCaP, and VCAP) were treated with anti-androgens and assessed for SLCO1B3 expression by qPCR analysis. Abiraterone treatment increased SLCO1B3 expression in 22Rv1 cells in vitro and in the 22Rv1 xenograft model in vivo. MicroRNA profiling of abiraterone-treated 22Rv1 cells was performed using a NanoString nCounter miRNA panel followed by miRNA target prediction. TargetScan and miRanda prediction tools identified hsa-miR-579-3p as binding to the 3′-untranslated region (3′UTR) of the SLCO1B3. Using dual luciferase reporter assays, we verified that hsa-miR-579-3p indeed binds to the SLCO1B3 3′UTR and significantly inhibited SLCO1B3 reporter activity. Treatment with abiraterone significantly downregulated hsa-miR-579-3p, indicating its potential role in upregulating SLCO1B3 expression. In this study, we demonstrated a novel miRNA-mediated mechanism of abiraterone-induced SLCO1B3 expression, a transporter that is also responsible for driving androgen deprivation therapy resistance. Understanding mechanisms of abiraterone resistance mediated via differential miRNA expression will assist in the identification of potential miRNA biomarkers of treatment resistance and the development of future therapeutics.
format	article
author	Roberto H. Barbier Edel M. McCrea Kristi Y. Lee Jonathan D. Strope Emily N. Risdon Douglas K. Price Cindy H. Chau William D. Figg
author_facet	Roberto H. Barbier Edel M. McCrea Kristi Y. Lee Jonathan D. Strope Emily N. Risdon Douglas K. Price Cindy H. Chau William D. Figg
author_sort	Roberto H. Barbier
title	Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
title_short	Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
title_full	Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
title_fullStr	Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
title_full_unstemmed	Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
title_sort	abiraterone induces slco1b3 expression in prostate cancer via microrna-579-3p
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e06fd1fa19174341a92b77d01fce5e9c
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Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p

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