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Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To da...

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Autores principales: Hesham, Dina, El-Naggar, Shahenda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563716/
https://www.ncbi.nlm.nih.gov/pubmed/32971786
http://dx.doi.org/10.3390/genes11091108
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author Hesham, Dina
El-Naggar, Shahenda
author_facet Hesham, Dina
El-Naggar, Shahenda
author_sort Hesham, Dina
collection PubMed
description Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.
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spelling pubmed-75637162020-10-27 Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes Hesham, Dina El-Naggar, Shahenda Genes (Basel) Article Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets. MDPI 2020-09-22 /pmc/articles/PMC7563716/ /pubmed/32971786 http://dx.doi.org/10.3390/genes11091108 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hesham, Dina
El-Naggar, Shahenda
Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title_full Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title_fullStr Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title_full_unstemmed Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title_short Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes
title_sort transcriptomic analysis revealed an emerging role of alternative splicing in embryonal tumor with multilayered rosettes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563716/
https://www.ncbi.nlm.nih.gov/pubmed/32971786
http://dx.doi.org/10.3390/genes11091108
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