Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Abstract Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain i...

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Autores principales: Tatiana Altadill, Tyrone M. Dowdy, Kirandeep Gill, Armando Reques, Smrithi S. Menon, Cristian P. Moiola, Carlos Lopez-Gil, Eva Coll, Xavier Matias-Guiu, Silvia Cabrera, Angel Garcia, Jaume Reventos, Stephen W. Byers, Antonio Gil-Moreno, Amrita K. Cheema, Eva Colas
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:3bb239e64b3648ca92e1d93bdc810fd32021-12-02T15:06:02ZMetabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis10.1038/s41598-017-09169-22045-2322https://doaj.org/article/3bb239e64b3648ca92e1d93bdc810fd32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09169-2https://doaj.org/toc/2045-2322Abstract Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.Tatiana AltadillTyrone M. DowdyKirandeep GillArmando RequesSmrithi S. MenonCristian P. MoiolaCarlos Lopez-GilEva CollXavier Matias-GuiuSilvia CabreraAngel GarciaJaume ReventosStephen W. ByersAntonio Gil-MorenoAmrita K. CheemaEva ColasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tatiana Altadill
Tyrone M. Dowdy
Kirandeep Gill
Armando Reques
Smrithi S. Menon
Cristian P. Moiola
Carlos Lopez-Gil
Eva Coll
Xavier Matias-Guiu
Silvia Cabrera
Angel Garcia
Jaume Reventos
Stephen W. Byers
Antonio Gil-Moreno
Amrita K. Cheema
Eva Colas
Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
description Abstract Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.
format article
author Tatiana Altadill
Tyrone M. Dowdy
Kirandeep Gill
Armando Reques
Smrithi S. Menon
Cristian P. Moiola
Carlos Lopez-Gil
Eva Coll
Xavier Matias-Guiu
Silvia Cabrera
Angel Garcia
Jaume Reventos
Stephen W. Byers
Antonio Gil-Moreno
Amrita K. Cheema
Eva Colas
author_facet Tatiana Altadill
Tyrone M. Dowdy
Kirandeep Gill
Armando Reques
Smrithi S. Menon
Cristian P. Moiola
Carlos Lopez-Gil
Eva Coll
Xavier Matias-Guiu
Silvia Cabrera
Angel Garcia
Jaume Reventos
Stephen W. Byers
Antonio Gil-Moreno
Amrita K. Cheema
Eva Colas
author_sort Tatiana Altadill
title Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
title_short Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
title_full Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
title_fullStr Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
title_full_unstemmed Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis
title_sort metabolomic and lipidomic profiling identifies the role of the rna editing pathway in endometrial carcinogenesis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3bb239e64b3648ca92e1d93bdc810fd3
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