Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.

MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular me...

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Autores principales:	Wenjuan Mo, Jiyuan Zhang, Xia Li, Delong Meng, Yun Gao, Shu Yang, Xuechao Wan, Caihong Zhou, Fenghua Guo, Yan Huang, Stefano Amente, Enrico V Avvedimento, Yi Xie, Yao Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb8c5554905f4f3288b689628e73d4cc
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spelling	oai:doaj.org-article:bb8c5554905f4f3288b689628e73d4cc2021-11-18T07:56:26ZIdentification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.1932-620310.1371/journal.pone.0056592https://doaj.org/article/bb8c5554905f4f3288b689628e73d4cc2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23451058/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen's growth restriction effect on normal prostate tissue.Wenjuan MoJiyuan ZhangXia LiDelong MengYun GaoShu YangXuechao WanCaihong ZhouFenghua GuoYan HuangStefano AmenteEnrico V AvvedimentoYi XieYao LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56592 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenjuan Mo Jiyuan Zhang Xia Li Delong Meng Yun Gao Shu Yang Xuechao Wan Caihong Zhou Fenghua Guo Yan Huang Stefano Amente Enrico V Avvedimento Yi Xie Yao Li Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
description	MicroRNAs (miRNAs) have been recognized as significantly involved in prostate cancer (PCa). Since androgen receptor (AR) plays a central role in PCa carcinogenesis and progression, it is imperative to systematically elucidate the causal association between AR and miRNAs, focusing on the molecular mechanisms by which miRNAs mediate AR signalling. In this study, we performed a series of time-course microarrays to observe the dynamic genome-wide expressions of mRNAs and miRNAs in parallel in hormone-sensitive prostate cancer LNCaP cells stimulated by androgen. Accordingly, we introduced Response Score to identify AR target miRNAs, as well as Modulation Score to identify miRNA target mRNAs. Based on theoretical identification and experimental validation, novel mechanisms addressing cell viability in PCa were unravelled for 3 miRNAs newly recognized as AR targets. (1) miR-19a is directly up-regulated by AR, and represses SUZ12, RAB13, SC4MOL, PSAP and ABCA1, respectively. (2) miR-27a is directly up-regulated by AR, and represses ABCA1 and PDS5B. (3) miR-133b is directly up-regulated by AR, and represses CDC2L5, PTPRK, RB1CC1, and CPNE3, respectively. Moreover, we found miR-133b is essential to PCa cell survival. Our study gives certain clues on miRNAs mediated AR signalling to cell viability by influencing critical pathways, especially by breaking through androgen's growth restriction effect on normal prostate tissue.
format	article
author	Wenjuan Mo Jiyuan Zhang Xia Li Delong Meng Yun Gao Shu Yang Xuechao Wan Caihong Zhou Fenghua Guo Yan Huang Stefano Amente Enrico V Avvedimento Yi Xie Yao Li
author_facet	Wenjuan Mo Jiyuan Zhang Xia Li Delong Meng Yun Gao Shu Yang Xuechao Wan Caihong Zhou Fenghua Guo Yan Huang Stefano Amente Enrico V Avvedimento Yi Xie Yao Li
author_sort	Wenjuan Mo
title	Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
title_short	Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
title_full	Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
title_fullStr	Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
title_full_unstemmed	Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
title_sort	identification of novel ar-targeted micrornas mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/bb8c5554905f4f3288b689628e73d4cc
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Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer.

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