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Article: Overexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer

TitleOverexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer
Authors
Issue Date2017
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2017, v. 8, p. 47020-47036 How to Cite?
AbstractThe identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues. In addition, ATF3 overexpression associated with a regulatory molecular signature, and its functions are related to the pathogenic development of CRC. Furthermore, putative ATF3 regulatory elements were identified within the promoters of ATF3 target genes and were confirmed by ChIP-Seq. Critically, in higher ATF3 expression cell lines (HCT116 and RKO) with CRISPR/Cas9 mediated ATF3 knock out, we are able to show that ATF3 target genes such as CEACAM1, DUSP14, HDC, HLF and ULBP2, are required for invasion and proliferation, and they are robustly linked with poor prognosis in CRC. Our findings have important implications for CRC tumorigenesis and may be exploited for diagnostic and therapeutic purposes.
Persistent Identifierhttp://hdl.handle.net/10722/240968
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294

 

DC FieldValueLanguage
dc.contributor.authorYan, F-
dc.contributor.authorYing, L-
dc.contributor.authorLi, X-
dc.contributor.authorQiao, B-
dc.contributor.authorMeng, Q-
dc.contributor.authorYu, L-
dc.contributor.authorYuan, X-
dc.contributor.authorRen, ST-
dc.contributor.authorChan, DW-
dc.contributor.authorShi, L-
dc.contributor.authorNi, P-
dc.contributor.authorWang, X-
dc.contributor.authorXu, D-
dc.contributor.authorHu, Y-
dc.date.accessioned2017-05-22T09:20:19Z-
dc.date.available2017-05-22T09:20:19Z-
dc.date.issued2017-
dc.identifier.citationOncotarget, 2017, v. 8, p. 47020-47036-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/240968-
dc.description.abstractThe identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues. In addition, ATF3 overexpression associated with a regulatory molecular signature, and its functions are related to the pathogenic development of CRC. Furthermore, putative ATF3 regulatory elements were identified within the promoters of ATF3 target genes and were confirmed by ChIP-Seq. Critically, in higher ATF3 expression cell lines (HCT116 and RKO) with CRISPR/Cas9 mediated ATF3 knock out, we are able to show that ATF3 target genes such as CEACAM1, DUSP14, HDC, HLF and ULBP2, are required for invasion and proliferation, and they are robustly linked with poor prognosis in CRC. Our findings have important implications for CRC tumorigenesis and may be exploited for diagnostic and therapeutic purposes.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleOverexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer-
dc.typeArticle-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.authorityChan, DW=rp00543-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.16638-
dc.identifier.pmid28402947-
dc.identifier.hkuros272093-
dc.identifier.volume8-
dc.identifier.spage47020-
dc.identifier.epage47036-
dc.publisher.placeUnited States-

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