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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doaj-3bb239e64b3648ca92e1d93bdc810fd32020-12-08T02:37:11ZengNature Publishing GroupScientific Reports2045-23222017-08-017111310.1038/s41598-017-09169-2Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial CarcinogenesisTatiana Altadill0Tyrone M. Dowdy1Kirandeep Gill2Armando Reques3Smrithi S. Menon4Cristian P. Moiola5Carlos Lopez-Gil6Eva Coll7Xavier Matias-Guiu8Silvia Cabrera9Angel Garcia10Jaume Reventos11Stephen W. Byers12Antonio Gil-Moreno13Amrita K. Cheema14Eva Colas15Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaDepartment of Oncology, Georgetown University Medical CenterDepartment of Oncology, Georgetown University Medical CenterPathology Department, Vall Hebron University HospitalDepartment of Oncology, Georgetown University Medical CenterBiomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaBiomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaBiomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPathological Oncology Group and Pathology Department, University Hospital Arnau de Vilanova, and University Hospital Bellvitge, IRBLLEIDA and Idibell, University of LleidaGynecological Oncology Department, Vall Hebron University HospitalPathology Department, Vall Hebron University HospitalBiomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaDepartment of Oncology, Georgetown University Medical CenterPathology Department, Vall Hebron University HospitalDepartment of Oncology, Georgetown University Medical CenterBiomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaAbstract 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.https://doi.org/10.1038/s41598-017-09169-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-09169-2 |
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