Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression

Abstract Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epith...

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Autores principales:	Matjaz Rokavec, Markus Kaller, David Horst, Heiko Hermeking
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/688cc78b6434435a850ee3cdf62c3d60
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spelling	oai:doaj.org-article:688cc78b6434435a850ee3cdf62c3d602021-12-02T16:07:48ZPan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression10.1038/s41598-017-04234-22045-2322https://doaj.org/article/688cc78b6434435a850ee3cdf62c3d602017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04234-2https://doaj.org/toc/2045-2322Abstract Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epithelial and 4 mesenchymal state-associated mRNAs. Among the identified epithelial cell state-associated factors, down-regulation of the RBM47 (RNA binding motif protein 47) mRNA displayed the most significant association with metastasis and poor survival in multiple cohorts of colorectal cancer (CRC) patients. Moreover, decreased RBM47 protein expression was associated with metastasis in a cohort of primary CRCs. RBM47 was directly suppressed during EMT induced by IL6-activated STAT3 or ectopic SNAIL and SLUG expression via conserved binding motifs of these factors within the RBM47 promoter. Moreover, RNAi-mediated down-regulation of RBM47 in CRC lines resulted in increased cell migration, invasion and metastases formation. As demonstrated by the example of RBM47, the EMT-associated signature characterized here allows to identify biomarkers for predicting clinical outcome of CRC and presumably other cancer entities. In addition, our functional analysis of RBM47 shows that the down-regulation of RBM47 during CRC progression may promote EMT and metastasis.Matjaz RokavecMarkus KallerDavid HorstHeiko HermekingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matjaz Rokavec Markus Kaller David Horst Heiko Hermeking Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
description	Abstract Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epithelial and 4 mesenchymal state-associated mRNAs. Among the identified epithelial cell state-associated factors, down-regulation of the RBM47 (RNA binding motif protein 47) mRNA displayed the most significant association with metastasis and poor survival in multiple cohorts of colorectal cancer (CRC) patients. Moreover, decreased RBM47 protein expression was associated with metastasis in a cohort of primary CRCs. RBM47 was directly suppressed during EMT induced by IL6-activated STAT3 or ectopic SNAIL and SLUG expression via conserved binding motifs of these factors within the RBM47 promoter. Moreover, RNAi-mediated down-regulation of RBM47 in CRC lines resulted in increased cell migration, invasion and metastases formation. As demonstrated by the example of RBM47, the EMT-associated signature characterized here allows to identify biomarkers for predicting clinical outcome of CRC and presumably other cancer entities. In addition, our functional analysis of RBM47 shows that the down-regulation of RBM47 during CRC progression may promote EMT and metastasis.
format	article
author	Matjaz Rokavec Markus Kaller David Horst Heiko Hermeking
author_facet	Matjaz Rokavec Markus Kaller David Horst Heiko Hermeking
author_sort	Matjaz Rokavec
title	Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
title_short	Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
title_full	Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
title_fullStr	Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
title_full_unstemmed	Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression
title_sort	pan-cancer emt-signature identifies rbm47 down-regulation during colorectal cancer progression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/688cc78b6434435a850ee3cdf62c3d60
work_keys_str_mv	AT matjazrokavec pancanceremtsignatureidentifiesrbm47downregulationduringcolorectalcancerprogression AT markuskaller pancanceremtsignatureidentifiesrbm47downregulationduringcolorectalcancerprogression AT davidhorst pancanceremtsignatureidentifiesrbm47downregulationduringcolorectalcancerprogression AT heikohermeking pancanceremtsignatureidentifiesrbm47downregulationduringcolorectalcancerprogression
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Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression

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