Editome landscape of CCM-derived endothelial cells

By regulating several phases of gene expression, RNA editing modifications contribute to maintaining physiological RNA expression levels. RNA editing dysregulation can affect RNA molecule half-life, coding/noncoding RNA interaction, alternative splicing, and circular RNA biogenesis. Impaired RNA edi...

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Main Authors: Concetta Scimone, Simona Alibrandi, Luigi Donato, Concetta Alafaci, Antonino Germanò, Sergio L. Vinci, Rosalia D’Angelo, Antonina Sidoti
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:RNA Biology
Subjects:
Online Access:http://dx.doi.org/10.1080/15476286.2022.2091306
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author Concetta Scimone
Simona Alibrandi
Luigi Donato
Concetta Alafaci
Antonino Germanò
Sergio L. Vinci
Rosalia D’Angelo
Antonina Sidoti
author_facet Concetta Scimone
Simona Alibrandi
Luigi Donato
Concetta Alafaci
Antonino Germanò
Sergio L. Vinci
Rosalia D’Angelo
Antonina Sidoti
author_sort Concetta Scimone
collection DOAJ
description By regulating several phases of gene expression, RNA editing modifications contribute to maintaining physiological RNA expression levels. RNA editing dysregulation can affect RNA molecule half-life, coding/noncoding RNA interaction, alternative splicing, and circular RNA biogenesis. Impaired RNA editing has been observed in several pathological conditions, including cancer and Alzheimer’s disease. No data has been published yet on the editome profile of endothelial cells (ECs) isolated from human cerebral cavernous malformation (CCM) lesions. Here, we describe a landscape of editome modifications in sporadic CCM-derived ECs (CCM-ECs) by comparing editing events with those observed in human brain microvascular endothelial cells (HBMECs). With a whole transcriptome-based variant calling pipeline, we identified differential edited genes in CCM-ECs that were enriched in pathways related to angiogenesis, apoptosis and cell survival, inflammation and, in particular, to thrombin signalling mediated by protease-activated receptors and non-canonical Wnt signalling. These pathways, not yet associated to CCM development, could be a novel field for further investigations on CCM molecular mechanisms. Moreover, enrichment analysis of differentially edited miRNAs suggested additional small noncoding transcripts to consider for development of targeted therapies.
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spelling doaj.art-e0b49f6d91e04dc791ebe92e6963e43e2023-12-05T16:09:51ZengTaylor & Francis GroupRNA Biology1547-62861555-85842022-12-0119185286510.1080/15476286.2022.20913062091306Editome landscape of CCM-derived endothelial cellsConcetta Scimone0Simona Alibrandi1Luigi Donato2Concetta Alafaci3Antonino Germanò4Sergio L. Vinci5Rosalia D’Angelo6Antonina Sidoti7University of MessinaUniversity of MessinaUniversity of MessinaUniversity of MessinaUniversity of MessinaUniversity of MessinaUniversity of MessinaUniversity of MessinaBy regulating several phases of gene expression, RNA editing modifications contribute to maintaining physiological RNA expression levels. RNA editing dysregulation can affect RNA molecule half-life, coding/noncoding RNA interaction, alternative splicing, and circular RNA biogenesis. Impaired RNA editing has been observed in several pathological conditions, including cancer and Alzheimer’s disease. No data has been published yet on the editome profile of endothelial cells (ECs) isolated from human cerebral cavernous malformation (CCM) lesions. Here, we describe a landscape of editome modifications in sporadic CCM-derived ECs (CCM-ECs) by comparing editing events with those observed in human brain microvascular endothelial cells (HBMECs). With a whole transcriptome-based variant calling pipeline, we identified differential edited genes in CCM-ECs that were enriched in pathways related to angiogenesis, apoptosis and cell survival, inflammation and, in particular, to thrombin signalling mediated by protease-activated receptors and non-canonical Wnt signalling. These pathways, not yet associated to CCM development, could be a novel field for further investigations on CCM molecular mechanisms. Moreover, enrichment analysis of differentially edited miRNAs suggested additional small noncoding transcripts to consider for development of targeted therapies.http://dx.doi.org/10.1080/15476286.2022.2091306cerebral cavernous malformationeditome profileprotease-activated receptor signallingrna sequencing analysisdifferentially edited genes
spellingShingle Concetta Scimone
Simona Alibrandi
Luigi Donato
Concetta Alafaci
Antonino Germanò
Sergio L. Vinci
Rosalia D’Angelo
Antonina Sidoti
Editome landscape of CCM-derived endothelial cells
RNA Biology
cerebral cavernous malformation
editome profile
protease-activated receptor signalling
rna sequencing analysis
differentially edited genes
title Editome landscape of CCM-derived endothelial cells
title_full Editome landscape of CCM-derived endothelial cells
title_fullStr Editome landscape of CCM-derived endothelial cells
title_full_unstemmed Editome landscape of CCM-derived endothelial cells
title_short Editome landscape of CCM-derived endothelial cells
title_sort editome landscape of ccm derived endothelial cells
topic cerebral cavernous malformation
editome profile
protease-activated receptor signalling
rna sequencing analysis
differentially edited genes
url http://dx.doi.org/10.1080/15476286.2022.2091306
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