miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster

Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell...

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Autores principales:	Yan Sweat, Ryan J. Ries, Mason Sweat, Dan Su, Fan Shao, Steven Eliason, Brad A. Amendt
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	miR-17 plasmid-based microRNA inhibitor system (PMIS) thyroid cancer miR-17-92 cluster miR mouse model miR-17 tumor suppressor Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/098fbd2b208b4b2cb254042c56488a4d
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spelling	oai:doaj.org-article:098fbd2b208b4b2cb254042c56488a4d2021-11-12T04:31:14ZmiR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster2162-253110.1016/j.omtn.2021.10.021https://doaj.org/article/098fbd2b208b4b2cb254042c56488a4d2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S216225312100264Xhttps://doaj.org/toc/2162-2531Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four miR-17-92 families were oncogenic, we uncovered a novel role for miR-17 as a tumor suppressor in vitro and in vivo. Surprisingly, miR-17 inhibition increased expression of the miR-17-92 cluster and significantly increased the levels of the miR-18a and miR-19a mature miRs. miR-17 inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. miR-17 regulates MYCN and c-MYC expression in SW579 cells, and the inhibition of miR-17 increased MYCN and c-MYC expression, which increased pri-miR-17-92 transcripts. Thus, inhibition of miR-17 activated the expression of the oncogenic miRs, miR-18a and miR-19a. While many cancers express high levels of miR-17, linking it with tumorigenesis, we demonstrate that miR-17 inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other miR-17-92 family members and genes to induce cancer progression.Yan SweatRyan J. RiesMason SweatDan SuFan ShaoSteven EliasonBrad A. AmendtElsevierarticlemiR-17plasmid-based microRNA inhibitor system (PMIS)thyroid cancermiR-17-92 clustermiR mouse modelmiR-17 tumor suppressorTherapeutics. PharmacologyRM1-950ENMolecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1148-1158 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-17 plasmid-based microRNA inhibitor system (PMIS) thyroid cancer miR-17-92 cluster miR mouse model miR-17 tumor suppressor Therapeutics. Pharmacology RM1-950
spellingShingle	miR-17 plasmid-based microRNA inhibitor system (PMIS) thyroid cancer miR-17-92 cluster miR mouse model miR-17 tumor suppressor Therapeutics. Pharmacology RM1-950 Yan Sweat Ryan J. Ries Mason Sweat Dan Su Fan Shao Steven Eliason Brad A. Amendt miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
description	Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four miR-17-92 families were oncogenic, we uncovered a novel role for miR-17 as a tumor suppressor in vitro and in vivo. Surprisingly, miR-17 inhibition increased expression of the miR-17-92 cluster and significantly increased the levels of the miR-18a and miR-19a mature miRs. miR-17 inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. miR-17 regulates MYCN and c-MYC expression in SW579 cells, and the inhibition of miR-17 increased MYCN and c-MYC expression, which increased pri-miR-17-92 transcripts. Thus, inhibition of miR-17 activated the expression of the oncogenic miRs, miR-18a and miR-19a. While many cancers express high levels of miR-17, linking it with tumorigenesis, we demonstrate that miR-17 inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other miR-17-92 family members and genes to induce cancer progression.
format	article
author	Yan Sweat Ryan J. Ries Mason Sweat Dan Su Fan Shao Steven Eliason Brad A. Amendt
author_facet	Yan Sweat Ryan J. Ries Mason Sweat Dan Su Fan Shao Steven Eliason Brad A. Amendt
author_sort	Yan Sweat
title	miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
title_short	miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
title_full	miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
title_fullStr	miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
title_full_unstemmed	miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
title_sort	mir-17 acts as a tumor suppressor by negatively regulating the mir-17-92 cluster
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/098fbd2b208b4b2cb254042c56488a4d
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_version_	1718431270625607680

miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster

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