Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer

Abstract MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined...

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Autores principales:	Binod Kumar, Avi Z. Rosenberg, Su Mi Choi, Karen Fox-Talbot, Angelo M. De Marzo, Larisa Nonn, W. Nathaniel Brennen, Luigi Marchionni, Marc K. Halushka, Shawn E. Lupold
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a8d5bc00c9b474db0d4de545fbb6069
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spelling	oai:doaj.org-article:6a8d5bc00c9b474db0d4de545fbb60692021-12-02T16:08:24ZCell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer10.1038/s41598-018-25320-z2045-2322https://doaj.org/article/6a8d5bc00c9b474db0d4de545fbb60692018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25320-zhttps://doaj.org/toc/2045-2322Abstract MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.Binod KumarAvi Z. RosenbergSu Mi ChoiKaren Fox-TalbotAngelo M. De MarzoLarisa NonnW. Nathaniel BrennenLuigi MarchionniMarc K. HalushkaShawn E. LupoldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Binod Kumar Avi Z. Rosenberg Su Mi Choi Karen Fox-Talbot Angelo M. De Marzo Larisa Nonn W. Nathaniel Brennen Luigi Marchionni Marc K. Halushka Shawn E. Lupold Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
description	Abstract MiR-1 and miR-143 are frequently reduced in human prostate cancer (PCa), while miR-141 and miR-21 are frequently elevated. Consequently, these miRNAs have been studied as cell-autonomous tumor suppressors and oncogenes. However, the cell-type specificity of these miRNAs is not well defined in prostate tissue. Through two different microdissection techniques, and droplet digital RT-PCR, we quantified these miRNAs in the stroma and epithelium of radical prostatectomy specimens. In contrast to their purported roles as cell-autonomous tumor suppressors, we found miR-1 and miR-143 expression to be predominantly stromal. Conversely, miR-141 was predominantly epithelial. miR-21 was detected in both stroma and epithelium. Strikingly, the levels of miR-1 and miR-143 were significantly reduced in tumor-associated stroma, but not tumor epithelium. Gene expression analyses in human cell lines, tissues, and prostate-derived stromal cultures support the cell-type selective expression of miR-1, miR-141, and miR-143. Analyses of the PCa Genome Atlas (TCGA-PRAD) showed a strong positive correlation between stromal markers and miR-1 and miR-143, and a strong negative correlation between stromal markers and miR-141. In these tumors, loss of miR-1 and gain of miR-21 was highly associated with biochemical recurrence. These data shed new light on stromal and epithelial miRNA expression in the PCa tumor microenvironment.
format	article
author	Binod Kumar Avi Z. Rosenberg Su Mi Choi Karen Fox-Talbot Angelo M. De Marzo Larisa Nonn W. Nathaniel Brennen Luigi Marchionni Marc K. Halushka Shawn E. Lupold
author_facet	Binod Kumar Avi Z. Rosenberg Su Mi Choi Karen Fox-Talbot Angelo M. De Marzo Larisa Nonn W. Nathaniel Brennen Luigi Marchionni Marc K. Halushka Shawn E. Lupold
author_sort	Binod Kumar
title	Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
title_short	Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
title_full	Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
title_fullStr	Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
title_full_unstemmed	Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer
title_sort	cell-type specific expression of oncogenic and tumor suppressive micrornas in the human prostate and prostate cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6a8d5bc00c9b474db0d4de545fbb6069
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Cell-type specific expression of oncogenic and tumor suppressive microRNAs in the human prostate and prostate cancer

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