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Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer
Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited...
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Published in: | Biochemical and biophysical research communications 2015-08, Vol.463 (4), p.961-967 |
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description | Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer.
[Display omitted]
•Identification of new target genes of FOXA2.•Identifications of novel interaction proteins of FOXA2.•Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer. |
doi_str_mv | 10.1016/j.bbrc.2015.06.042 |
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[Display omitted]
•Identification of new target genes of FOXA2.•Identifications of novel interaction proteins of FOXA2.•Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.06.042</identifier><identifier>PMID: 26093302</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADHESION ; APOPTOSIS ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - pathology ; CELL CYCLE ; Cell Line, Tumor ; Chromatin Immunoprecipitation ; DEATH ; FOXA2 ; Gene Expression Regulation - physiology ; Gene Regulatory Networks ; GENES ; HEAT ; HEAT-SHOCK PROTEINS ; Hepatocyte Nuclear Factor 3-beta - physiology ; Humans ; Lung Neoplasms - genetics ; Lung Neoplasms - pathology ; LUNGS ; MOLECULES ; NEOPLASMS ; Novel binding proteins ; Novel target genes ; PROMOTERS ; RECEPTORS ; SCREENING ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; THERAPY ; TRANSCRIPTION FACTORS ; Transcription, Genetic - physiology ; Transcriptional regulatory network</subject><ispartof>Biochemical and biophysical research communications, 2015-08, Vol.463 (4), p.961-967</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-c1096c9c742403762512460ff55ed70fb3f27b7bda5b8ef3cf1600810aa8b8053</citedby><cites>FETCH-LOGICAL-c520t-c1096c9c742403762512460ff55ed70fb3f27b7bda5b8ef3cf1600810aa8b8053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26093302$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22462155$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Jang, Sang-Min</creatorcontrib><creatorcontrib>An, Joo-Hee</creatorcontrib><creatorcontrib>Kim, Chul-Hong</creatorcontrib><creatorcontrib>Kim, Jung-Woong</creatorcontrib><creatorcontrib>Choi, Kyung-Hee</creatorcontrib><title>Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer.
[Display omitted]
•Identification of new target genes of FOXA2.•Identifications of novel interaction proteins of FOXA2.•Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADHESION</subject><subject>APOPTOSIS</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>CELL CYCLE</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Immunoprecipitation</subject><subject>DEATH</subject><subject>FOXA2</subject><subject>Gene Expression Regulation - physiology</subject><subject>Gene Regulatory Networks</subject><subject>GENES</subject><subject>HEAT</subject><subject>HEAT-SHOCK PROTEINS</subject><subject>Hepatocyte Nuclear Factor 3-beta - physiology</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - pathology</subject><subject>LUNGS</subject><subject>MOLECULES</subject><subject>NEOPLASMS</subject><subject>Novel binding proteins</subject><subject>Novel target genes</subject><subject>PROMOTERS</subject><subject>RECEPTORS</subject><subject>SCREENING</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>THERAPY</subject><subject>TRANSCRIPTION FACTORS</subject><subject>Transcription, Genetic - physiology</subject><subject>Transcriptional regulatory network</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kUFv1DAUhC1ERZeWP8ABReLCJemzEzsbiUtVUUCq1Esr9WY5L8_FS9ZebAfEv8dhC-LExc-Hb0ajGcZec2g4cHWxa8YxYiOAywZUA514xjYcBqgFh-452wCAqsXAH07Zy5R2AJx3anjBToWCoW1BbNh0F41PGN0hu-ArazCHWF3fPlyKGslnijRV-V_GzFWkx2U2vwWe8o8Qv1aufIOv097Mc4VUnnnxjxUajxTP2Yk1c6JXT_eM3V9_uLv6VN_cfvx8dXlToxSQayzZFQ7Yd6KDtldCctEpsFZKmnqwY2tFP_bjZOS4Jdui5Qpgy8GY7bgF2Z6xt0ffkLLTCV0m_ILBe8KsRfESXK7UuyN1iOHbQinrvUtrZOMpLElzNUjet2rgBRVHFGNIKZLVh-j2Jv7UHPS6gd7pdQO9bqBB6bJBEb158l_GPU1_JX9KL8D7I0Cli--O4hqVSlGTi2vSKbj_-f8CsUmX0g</recordid><startdate>20150807</startdate><enddate>20150807</enddate><creator>Jang, Sang-Min</creator><creator>An, Joo-Hee</creator><creator>Kim, Chul-Hong</creator><creator>Kim, Jung-Woong</creator><creator>Choi, Kyung-Hee</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20150807</creationdate><title>Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer</title><author>Jang, Sang-Min ; An, Joo-Hee ; Kim, Chul-Hong ; Kim, Jung-Woong ; Choi, Kyung-Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-c1096c9c742403762512460ff55ed70fb3f27b7bda5b8ef3cf1600810aa8b8053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADHESION</topic><topic>APOPTOSIS</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>CELL CYCLE</topic><topic>Cell Line, Tumor</topic><topic>Chromatin Immunoprecipitation</topic><topic>DEATH</topic><topic>FOXA2</topic><topic>Gene Expression Regulation - physiology</topic><topic>Gene Regulatory Networks</topic><topic>GENES</topic><topic>HEAT</topic><topic>HEAT-SHOCK PROTEINS</topic><topic>Hepatocyte Nuclear Factor 3-beta - physiology</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - pathology</topic><topic>LUNGS</topic><topic>MOLECULES</topic><topic>NEOPLASMS</topic><topic>Novel binding proteins</topic><topic>Novel target genes</topic><topic>PROMOTERS</topic><topic>RECEPTORS</topic><topic>SCREENING</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>THERAPY</topic><topic>TRANSCRIPTION FACTORS</topic><topic>Transcription, Genetic - physiology</topic><topic>Transcriptional regulatory network</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jang, Sang-Min</creatorcontrib><creatorcontrib>An, Joo-Hee</creatorcontrib><creatorcontrib>Kim, Chul-Hong</creatorcontrib><creatorcontrib>Kim, Jung-Woong</creatorcontrib><creatorcontrib>Choi, Kyung-Hee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jang, Sang-Min</au><au>An, Joo-Hee</au><au>Kim, Chul-Hong</au><au>Kim, Jung-Woong</au><au>Choi, Kyung-Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-08-07</date><risdate>2015</risdate><volume>463</volume><issue>4</issue><spage>961</spage><epage>967</epage><pages>961-967</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Lung cancer is the leading cause of cancer-mediated death. Although various therapeutic approaches are used for lung cancer treatment, these mainly target the tumor suppressor p53 transcription factor, which is involved in apoptosis and cell cycle arrest. However, p53-targeted therapies have limited application in lung cancer, since p53 is found to be mutated in more than half of lung cancers. In this study, we propose tumor suppressor FOXA2 as an alternative target protein for therapies against lung cancer and reveal a possible FOXA2-centered transcriptional regulation network by identifying new target genes and binding partners of FOXA2 by using various screening techniques. The genes encoding Glu/Asp-rich carboxy-terminal domain 2 (CITED2), nuclear receptor subfamily 0, group B, member 2 (NR0B2), cell adhesion molecule 1 (CADM1) and BCL2-associated X protein (BAX) were identified as putative target genes of FOXA2. Additionally, the proteins including highly similar to heat shock protein HSP 90-beta (HSP90A), heat shock 70 kDa protein 1A variant (HSPA1A), histone deacetylase 1 (HDAC1) and HDAC3 were identified as novel interacting partners of FOXA2. Moreover, we showed that FOXA2-dependent promoter activation of BAX and p21 genes is significantly reduced via physical interactions between the identified binding partners and FOXA2. These results provide opportunities to understand the FOXA2-centered transcriptional regulation network and novel therapeutic targets to modulate this network in p53-deficient lung cancer.
[Display omitted]
•Identification of new target genes of FOXA2.•Identifications of novel interaction proteins of FOXA2.•Construction of FOXA2-centered transcriptional regulatory network in non-small cell lung cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26093302</pmid><doi>10.1016/j.bbrc.2015.06.042</doi><tpages>7</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES ADHESION APOPTOSIS Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - pathology CELL CYCLE Cell Line, Tumor Chromatin Immunoprecipitation DEATH FOXA2 Gene Expression Regulation - physiology Gene Regulatory Networks GENES HEAT HEAT-SHOCK PROTEINS Hepatocyte Nuclear Factor 3-beta - physiology Humans Lung Neoplasms - genetics Lung Neoplasms - pathology LUNGS MOLECULES NEOPLASMS Novel binding proteins Novel target genes PROMOTERS RECEPTORS SCREENING Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization THERAPY TRANSCRIPTION FACTORS Transcription, Genetic - physiology Transcriptional regulatory network |
title | Transcription factor FOXA2-centered transcriptional regulation network in non-small cell lung cancer |
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