Differentiated embryo chondrocyte plays a crucial role in DNA damage response via transcriptional regulation under hypoxic conditions

PloS One
Hideaki NakamuraKeiji Tanimoto

Abstract

Tumor hypoxia contributes to a biologically aggressive phenotype and therapeutic resistance. Recent studies have revealed that hypoxia reduces expression of several DNA damage recognition and repair (DRR) genes via both hypoxia-inducible factor (HIF)-independent and -dependent pathways, and this induced genomic instability in cancer cells. We show here that one of the HIF-target genes-differentiated embryo chondrocyte (DEC)-plays a role in DNA damage response via transcriptional repression. Comprehensive gene expression and database analyses have revealed systemic repression of DNA-DRR genes in cancer and non-cancer cells under hypoxic conditions. Hypoxic repression in typical cases was confirmed by quantitative RT-PCR and promoter reporter experiments, and knockdown experiments indicated the critical role of DEC2 in such repression. Assessment of histone H2AX phosphorylation revealed that recognition and repair of DNA double-strand breaks (DSBs) induced by bleomycin or γ-ray irradiation were attenuated; moreover, Cleaved Caspase-3 levels were decreased with pre-conditioning under hypoxia: opposing phenomena were ascertained by knockdown of DEC2. Finally, pre-conditioning under hypoxia decreased the sensitivity of cancer cells ...Continue Reading

References

Jun 1, 1994·Cancer Metastasis Reviews·B A Teicher
Mar 21, 2002·Nature Reviews. Cancer·Adrian L Harris
Oct 2, 2002·The Journal of Biological Chemistry·Kazuko MiyazakiYukio Kato
Oct 25, 2002·Nature·Sato HonmaKen-ichi Honma
Mar 8, 2003·The Journal of Biological Chemistry·Yuxin LiBingfang Yan
Apr 17, 2003·Molecular and Cellular Biology·Valia T MihaylovaPeter M Glazer
Aug 30, 2003·Oncogene·Nicholas C DenkoAmato J Giaccia
Sep 18, 2003·Nature Reviews. Cancer·Gregg L Semenza
Dec 16, 2003·Biochemical and Biophysical Research Communications·Takeshi KawamotoYukio Kato
Jan 20, 2004·Journal of Cell Science·Oliver Fleck, Olaf Nielsen
Feb 13, 2004·Bioinformatics·Laurent GautierRafael A Irizarry
Sep 16, 2004·Molecular and Cellular Biology·Ranjit S BindraPeter M Glazer
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Takuya NoguchiMasahiko Nishiyama
Dec 17, 2005·Cancer Research·Ranjit S BindraPeter M Glazer
Mar 4, 2006·Molecular Cancer Research : MCR·Rob CairnsNicholas Denko
Mar 21, 2006·Molecular Cancer Therapeutics·Masaaki KomatsuMasahiko Nishiyama
Sep 27, 2006·Oncogene·R S Bindra, P M Glazer
Feb 15, 2008·Nature Reviews. Cancer·Robert G Bristow, Richard P Hill
Sep 6, 2008·Nucleic Acids Research·Andrea KinnerGeorge Iliakis
Nov 14, 2008·Nature Reviews. Cancer·William M BonnerYves Pommier
Nov 4, 2009·Nature Reviews. Genetics·Urban LendahlLorenz Poellinger
Dec 17, 2009·FEBS Letters·Jian-Jun LiuReshma Taneja
Oct 23, 2010·Molecular Cell·Amar J MajmundarM Celeste Simon
May 25, 2011·Nature Reviews. Cancer·William R Wilson, Michael P Hay
Aug 13, 2011·The New England Journal of Medicine·Gregg L Semenza
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Erez FeigeDavid E Fisher
Nov 30, 2012·Nucleic Acids Research·Tanya BarrettAlexandra Soboleva
Nov 30, 2013·Nature Reviews. Drug Discovery·Chiara GorriniTak W Mak
Sep 25, 2014·Current Topics in Developmental Biology·Jin Rong OwReshma Taneja

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Citations

Jan 16, 2020·Biomedicines·Hidemasa Bono, Kiichi Hirota
May 22, 2021·Frontiers in Genetics·John P BrabsonLuisa Cimmino

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Datasets Mentioned

BETA
GPL570
GSE53012

Methods Mentioned

BETA
Transfection
Assay
PCR
electrophoresis
Knockdown
X-ray

Software Mentioned

ImageJ
BioConductor
CodeLink TM Expression Analysis
StatView
R
affy package
DAVID
DAVID Bioinformatics Resources

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