Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells

Abstract Prostate cancer (PCa) is dependent on the androgen receptor (AR). Advanced PCa is treated with an androgen deprivation therapy-based regimen; tumors develop resistance, although they typically remain AR-dependent. Expression of constitutively active AR variants lacking the ligand-binding do...

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Autores principales:	Manjul Rana, Jianrong Dong, Matthew J. Robertson, Cristian Coarfa, Nancy L. Weigel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d596508e4db041fab19ab78aa8fed1fd
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spelling	oai:doaj.org-article:d596508e4db041fab19ab78aa8fed1fd2021-12-02T14:12:40ZAndrogen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells10.1038/s41598-021-81164-02045-2322https://doaj.org/article/d596508e4db041fab19ab78aa8fed1fd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81164-0https://doaj.org/toc/2045-2322Abstract Prostate cancer (PCa) is dependent on the androgen receptor (AR). Advanced PCa is treated with an androgen deprivation therapy-based regimen; tumors develop resistance, although they typically remain AR-dependent. Expression of constitutively active AR variants lacking the ligand-binding domain including the variant AR-V7 contributes to this resistance. AR and AR-V7, as transcription factors, regulate many of the same genes, but also have unique activities. In this study, the capacity of the two AR isoforms to regulate splicing was examined. RNA-seq data from models that endogenously express AR and express AR-V7 in response to doxycycline were used. Both AR isoforms induced multiple changes in splicing and many changes were isoform-specific. Analyses of two endogenous genes, PGAP2 and TPD52, were performed to examine differential splicing. A novel exon that appears to be a novel transcription start site was preferentially induced by AR-V7 in PGAP2 although it is induced to a lesser extent by AR. The previously described AR induced promoter 2 usage that results in a novel protein derived from TPD52 (PrLZ) was not induced by AR-V7. AR, but not AR-V7, bound to a site proximal to promoter 2, and induction was found to depend on FOXA1.Manjul RanaJianrong DongMatthew J. RobertsonCristian CoarfaNancy L. WeigelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manjul Rana Jianrong Dong Matthew J. Robertson Cristian Coarfa Nancy L. Weigel Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
description	Abstract Prostate cancer (PCa) is dependent on the androgen receptor (AR). Advanced PCa is treated with an androgen deprivation therapy-based regimen; tumors develop resistance, although they typically remain AR-dependent. Expression of constitutively active AR variants lacking the ligand-binding domain including the variant AR-V7 contributes to this resistance. AR and AR-V7, as transcription factors, regulate many of the same genes, but also have unique activities. In this study, the capacity of the two AR isoforms to regulate splicing was examined. RNA-seq data from models that endogenously express AR and express AR-V7 in response to doxycycline were used. Both AR isoforms induced multiple changes in splicing and many changes were isoform-specific. Analyses of two endogenous genes, PGAP2 and TPD52, were performed to examine differential splicing. A novel exon that appears to be a novel transcription start site was preferentially induced by AR-V7 in PGAP2 although it is induced to a lesser extent by AR. The previously described AR induced promoter 2 usage that results in a novel protein derived from TPD52 (PrLZ) was not induced by AR-V7. AR, but not AR-V7, bound to a site proximal to promoter 2, and induction was found to depend on FOXA1.
format	article
author	Manjul Rana Jianrong Dong Matthew J. Robertson Cristian Coarfa Nancy L. Weigel
author_facet	Manjul Rana Jianrong Dong Matthew J. Robertson Cristian Coarfa Nancy L. Weigel
author_sort	Manjul Rana
title	Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
title_short	Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
title_full	Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
title_fullStr	Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
title_full_unstemmed	Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells
title_sort	androgen receptor and its splice variant, ar-v7, differentially induce mrna splicing in prostate cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d596508e4db041fab19ab78aa8fed1fd
work_keys_str_mv	AT manjulrana androgenreceptoranditssplicevariantarv7differentiallyinducemrnasplicinginprostatecancercells AT jianrongdong androgenreceptoranditssplicevariantarv7differentiallyinducemrnasplicinginprostatecancercells AT matthewjrobertson androgenreceptoranditssplicevariantarv7differentiallyinducemrnasplicinginprostatecancercells AT cristiancoarfa androgenreceptoranditssplicevariantarv7differentiallyinducemrnasplicinginprostatecancercells AT nancylweigel androgenreceptoranditssplicevariantarv7differentiallyinducemrnasplicinginprostatecancercells
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Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells

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