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The global landscape of intron retentions in lung adenocarcinoma

BACKGROUND: The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. METHODS: In this study, we exploited whole tran...

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Autores principales: Zhang, Qu, Li, Hua, Jin, Hong, Tan, Huibiao, Zhang, Jun, Sheng, Sitong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999986/
https://www.ncbi.nlm.nih.gov/pubmed/24646369
http://dx.doi.org/10.1186/1755-8794-7-15
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author Zhang, Qu
Li, Hua
Jin, Hong
Tan, Huibiao
Zhang, Jun
Sheng, Sitong
author_facet Zhang, Qu
Li, Hua
Jin, Hong
Tan, Huibiao
Zhang, Jun
Sheng, Sitong
author_sort Zhang, Qu
collection PubMed
description BACKGROUND: The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. METHODS: In this study, we exploited whole transcriptome sequencing data from five lung adenocarcinoma tissues and their matched normal tissues to interrogate intron retention, a less studied alternative splicing form which has profound structural and functional consequence by modifying open reading frame or inserting premature stop codons. RESULTS: Abundant intron retention events were found in both tumor and normal tissues, and 2,340 and 1,422 genes only contain tumor-specific retentions and normal-specific retentions, respectively. Combined with gene expression analysis, we showed that genes with tumor-specific retentions tend to be over-expressed in tumors, and the abundance of intron retention within genes is negatively related with gene expression, indicating the action of nonsense mediated decay. Further functional analysis demonstrated that genes with tumor-specific retentions include known lung cancer driver genes and are found enriched in pathways important in carcinogenesis. CONCLUSIONS: We hypothesize that intron retentions and consequent nonsense mediated decay may collectively counteract the over-expression of genes promoting cancer development. Identification of genes with tumor-specific retentions may also help develop targeted therapies.
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spelling pubmed-39999862014-05-08 The global landscape of intron retentions in lung adenocarcinoma Zhang, Qu Li, Hua Jin, Hong Tan, Huibiao Zhang, Jun Sheng, Sitong BMC Med Genomics Research Article BACKGROUND: The transcriptome complexity in an organism can be achieved by alternative splicing of precursor messenger RNAs. It has been revealed that alternations in mRNA splicing play an important role in a number of diseases including human cancers. METHODS: In this study, we exploited whole transcriptome sequencing data from five lung adenocarcinoma tissues and their matched normal tissues to interrogate intron retention, a less studied alternative splicing form which has profound structural and functional consequence by modifying open reading frame or inserting premature stop codons. RESULTS: Abundant intron retention events were found in both tumor and normal tissues, and 2,340 and 1,422 genes only contain tumor-specific retentions and normal-specific retentions, respectively. Combined with gene expression analysis, we showed that genes with tumor-specific retentions tend to be over-expressed in tumors, and the abundance of intron retention within genes is negatively related with gene expression, indicating the action of nonsense mediated decay. Further functional analysis demonstrated that genes with tumor-specific retentions include known lung cancer driver genes and are found enriched in pathways important in carcinogenesis. CONCLUSIONS: We hypothesize that intron retentions and consequent nonsense mediated decay may collectively counteract the over-expression of genes promoting cancer development. Identification of genes with tumor-specific retentions may also help develop targeted therapies. BioMed Central 2014-03-20 /pmc/articles/PMC3999986/ /pubmed/24646369 http://dx.doi.org/10.1186/1755-8794-7-15 Text en Copyright © 2014 Zhang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Qu
Li, Hua
Jin, Hong
Tan, Huibiao
Zhang, Jun
Sheng, Sitong
The global landscape of intron retentions in lung adenocarcinoma
title The global landscape of intron retentions in lung adenocarcinoma
title_full The global landscape of intron retentions in lung adenocarcinoma
title_fullStr The global landscape of intron retentions in lung adenocarcinoma
title_full_unstemmed The global landscape of intron retentions in lung adenocarcinoma
title_short The global landscape of intron retentions in lung adenocarcinoma
title_sort global landscape of intron retentions in lung adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999986/
https://www.ncbi.nlm.nih.gov/pubmed/24646369
http://dx.doi.org/10.1186/1755-8794-7-15
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