NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

Abstract Experimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent st...

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Autores principales:	Xuan Wang, Jun Cai, Lei Zhao, Dejun Zhang, Guojie Xu, Jianli Hu, Tao Zhang, Min Jin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2bb724ebe7fa40afa5c8af23431ffba0
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spelling	oai:doaj.org-article:2bb724ebe7fa40afa5c8af23431ffba02021-12-02T14:42:01ZNUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis10.1038/s41598-021-90700-x2045-2322https://doaj.org/article/2bb724ebe7fa40afa5c8af23431ffba02021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90700-xhttps://doaj.org/toc/2045-2322Abstract Experimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.Xuan WangJun CaiLei ZhaoDejun ZhangGuojie XuJianli HuTao ZhangMin JinNature 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 Xuan Wang Jun Cai Lei Zhao Dejun Zhang Guojie Xu Jianli Hu Tao Zhang Min Jin NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
description	Abstract Experimental and clinical studies over the past two decades have provided overwhelming evidence that human cancers, including prostate cancer (PCa), harbor cancer stem cells (CSCs) that sustain tumor growth, drive tumor progression and mediate therapy resistance and tumor relapse. Recent studies have also implicated NUMB as a PCa suppressor and an inhibitor of PCa stem cells (PCSCs); however, exactly how NUMB functions in these contexts remains unclear. Here, by employing bioinformatics analysis and luciferase assays and by conducting rescue experiments, we first show that NUMB is directly targeted by microRNA-9-5p (miR-9-5p), an oncogenic miR associated with poor prognosis in many malignancies. We further show that miR-9-5p levels are inversely correlated with NUMB expression in CD44+ PCSCs. miR-9-5p reduced NUMB expression and inhibited numerous PCSC properties including proliferation, migration, invasion as well as self-renewal. Strikingly, overexpression of NUMB in CD44+ PCSCs overcame all of the above PCSC properties enforced by miR-9-5p. Taken together, our results suggest that inhibiting the expression of the oncomiR miR-9-5p and overexpressing NUMB may represent novel therapeutic strategies to target PCSCs and PCa metastasis.
format	article
author	Xuan Wang Jun Cai Lei Zhao Dejun Zhang Guojie Xu Jianli Hu Tao Zhang Min Jin
author_facet	Xuan Wang Jun Cai Lei Zhao Dejun Zhang Guojie Xu Jianli Hu Tao Zhang Min Jin
author_sort	Xuan Wang
title	NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
title_short	NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
title_full	NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
title_fullStr	NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
title_full_unstemmed	NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis
title_sort	numb suppression by mir-9-5p enhances cd44+ prostate cancer stem cell growth and metastasis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2bb724ebe7fa40afa5c8af23431ffba0
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NUMB suppression by miR-9-5P enhances CD44+ prostate cancer stem cell growth and metastasis

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