Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells

Abstract Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hy...

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Autores principales:	Jian Han, Jia Li, Jolene Caifeng Ho, Grace Sushin Chia, Hiroyuki Kato, Sudhakar Jha, Henry Yang, Lorenz Poellinger, Kian Leong Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e8109a31875479182423eb5f4124d09
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spelling	oai:doaj.org-article:3e8109a31875479182423eb5f4124d092021-12-02T11:53:00ZHypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells10.1038/s41598-017-04333-02045-2322https://doaj.org/article/3e8109a31875479182423eb5f4124d092017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04333-0https://doaj.org/toc/2045-2322Abstract Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood. To identify and quantify hypoxia-induced alternative splicing events in human cancer cells, we performed whole transcriptome RNA-Seq in breast cancer cells that are known to provide robust transcriptional response to hypoxia. We found 2005 and 1684 alternative splicing events including intron retention, exon skipping and alternative first exon usage that were regulated by acute and chronic hypoxia where intron retention was the most dominant type of hypoxia-induced alternative splicing. Many of these genes are involved in cellular metabolism, transcriptional regulation, actin cytoskeleton organisation, cancer cell proliferation, migration and invasion, suggesting they may modulate or be involved in additional features of tumorigenic development that extend beyond the known functions of canonical full-length transcripts.Jian HanJia LiJolene Caifeng HoGrace Sushin ChiaHiroyuki KatoSudhakar JhaHenry YangLorenz PoellingerKian Leong LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jian Han Jia Li Jolene Caifeng Ho Grace Sushin Chia Hiroyuki Kato Sudhakar Jha Henry Yang Lorenz Poellinger Kian Leong Lee Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
description	Abstract Adaptation to hypoxia, a hallmark feature of many tumors, is an important driver of cancer cell survival, proliferation and the development of resistance to chemotherapy. Hypoxia-induced stabilization of hypoxia-inducible factors (HIFs) leads to transcriptional activation of a network of hypoxia target genes involved in angiogenesis, cell growth, glycolysis, DNA damage repair and apoptosis. Although the transcriptional targets of hypoxia have been characterized, the alternative splicing of transcripts that occurs during hypoxia and the roles they play in oncogenesis are much less understood. To identify and quantify hypoxia-induced alternative splicing events in human cancer cells, we performed whole transcriptome RNA-Seq in breast cancer cells that are known to provide robust transcriptional response to hypoxia. We found 2005 and 1684 alternative splicing events including intron retention, exon skipping and alternative first exon usage that were regulated by acute and chronic hypoxia where intron retention was the most dominant type of hypoxia-induced alternative splicing. Many of these genes are involved in cellular metabolism, transcriptional regulation, actin cytoskeleton organisation, cancer cell proliferation, migration and invasion, suggesting they may modulate or be involved in additional features of tumorigenic development that extend beyond the known functions of canonical full-length transcripts.
format	article
author	Jian Han Jia Li Jolene Caifeng Ho Grace Sushin Chia Hiroyuki Kato Sudhakar Jha Henry Yang Lorenz Poellinger Kian Leong Lee
author_facet	Jian Han Jia Li Jolene Caifeng Ho Grace Sushin Chia Hiroyuki Kato Sudhakar Jha Henry Yang Lorenz Poellinger Kian Leong Lee
author_sort	Jian Han
title	Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
title_short	Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
title_full	Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
title_fullStr	Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
title_full_unstemmed	Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells
title_sort	hypoxia is a key driver of alternative splicing in human breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3e8109a31875479182423eb5f4124d09
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Hypoxia is a Key Driver of Alternative Splicing in Human Breast Cancer Cells

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