Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC
Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we ide...
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| Veröffentlicht in: | Cancers 2019-07, Vol.11 (7), p.974 |
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| creator | Junjappa, Raghu Patil Kim, Hyun-Kyoung Park, Seong Yeol Bhattarai, Kashi Raj Kim, Kyung-Woon Soh, Jae-Won Kim, Hyung-Ryong Chae, Han-Jung |
| description | Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (-133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer. |
| doi_str_mv | 10.3390/cancers11070974 |
| format | Article |
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Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (-133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers11070974</identifier><identifier>PMID: 31336725</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Apoptosis ; Bax protein ; Binding sites ; Breast cancer ; Cancer ; Cell death ; Cloning ; Gene expression ; Gene regulation ; Genomes ; Immunohistochemistry ; Liver cancer ; Metastases ; Mutation ; Nuclear transport ; Physiology ; Polymerase chain reaction ; Prostate ; Prostate cancer ; Protein kinase C ; Reporter gene ; siRNA ; Sp1 protein ; Transcription factors</subject><ispartof>Cancers, 2019-07, Vol.11 (7), p.974</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-5151a45fd7b92c3aa8bf5dbc9b4df14e43b71e4a50f3e498be85f9ef9c177a183</citedby><cites>FETCH-LOGICAL-c421t-5151a45fd7b92c3aa8bf5dbc9b4df14e43b71e4a50f3e498be85f9ef9c177a183</cites><orcidid>0000-0003-4190-9889</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678130/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678130/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31336725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Junjappa, Raghu Patil</creatorcontrib><creatorcontrib>Kim, Hyun-Kyoung</creatorcontrib><creatorcontrib>Park, Seong Yeol</creatorcontrib><creatorcontrib>Bhattarai, Kashi Raj</creatorcontrib><creatorcontrib>Kim, Kyung-Woon</creatorcontrib><creatorcontrib>Soh, Jae-Won</creatorcontrib><creatorcontrib>Kim, Hyung-Ryong</creatorcontrib><creatorcontrib>Chae, Han-Jung</creatorcontrib><title>Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (-133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer.</description><subject>Apoptosis</subject><subject>Bax protein</subject><subject>Binding sites</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Cloning</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genomes</subject><subject>Immunohistochemistry</subject><subject>Liver cancer</subject><subject>Metastases</subject><subject>Mutation</subject><subject>Nuclear transport</subject><subject>Physiology</subject><subject>Polymerase chain reaction</subject><subject>Prostate</subject><subject>Prostate cancer</subject><subject>Protein kinase C</subject><subject>Reporter gene</subject><subject>siRNA</subject><subject>Sp1 protein</subject><subject>Transcription factors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1LAzEQhoMoWrRnb7LgxUs1ySSbjQdFix_FFgXrOWSziW7ZJjVpi_57t7SKOpcZmHeemeFF6JDgUwCJz4z2xsZECBZYCraFOhQL2stzybZ_1Xuom9IEtwFARC520R4QgFxQ3kGXNx-zaFOqg8-Cy8aj68Eoz2qf9dfw82z8ZrOBX4ZmaafWz1eq5xnJtK-yp4f-Adpxukm2u8n76OX2Zty_7w0f7wb9q2HPMErmPU440Yy7SpSSGtC6KB2vSiNLVjnCLINSEMs0xw4sk0VpC-6kddIQITQpYB9drLmzRTm1lWkvibpRs1hPdfxUQdfqb8fXb-o1LFWei4IAbgEnG0AM7wub5mpaJ2ObRnsbFklRmgNQkLDadfxPOgmL6Nv3FOVMMCk5XwHP1ioTQ0rRup9jCFYrf9Q_f9qJo98__Oi_3YAvOPmLKg</recordid><startdate>20190711</startdate><enddate>20190711</enddate><creator>Junjappa, Raghu Patil</creator><creator>Kim, Hyun-Kyoung</creator><creator>Park, Seong Yeol</creator><creator>Bhattarai, Kashi Raj</creator><creator>Kim, Kyung-Woon</creator><creator>Soh, Jae-Won</creator><creator>Kim, Hyung-Ryong</creator><creator>Chae, Han-Jung</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4190-9889</orcidid></search><sort><creationdate>20190711</creationdate><title>Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC</title><author>Junjappa, Raghu Patil ; Kim, Hyun-Kyoung ; Park, Seong Yeol ; Bhattarai, Kashi Raj ; Kim, Kyung-Woon ; Soh, Jae-Won ; Kim, Hyung-Ryong ; Chae, Han-Jung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-5151a45fd7b92c3aa8bf5dbc9b4df14e43b71e4a50f3e498be85f9ef9c177a183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Apoptosis</topic><topic>Bax protein</topic><topic>Binding sites</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell death</topic><topic>Cloning</topic><topic>Gene expression</topic><topic>Gene regulation</topic><topic>Genomes</topic><topic>Immunohistochemistry</topic><topic>Liver cancer</topic><topic>Metastases</topic><topic>Mutation</topic><topic>Nuclear transport</topic><topic>Physiology</topic><topic>Polymerase chain reaction</topic><topic>Prostate</topic><topic>Prostate cancer</topic><topic>Protein kinase C</topic><topic>Reporter gene</topic><topic>siRNA</topic><topic>Sp1 protein</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Junjappa, Raghu Patil</creatorcontrib><creatorcontrib>Kim, Hyun-Kyoung</creatorcontrib><creatorcontrib>Park, Seong Yeol</creatorcontrib><creatorcontrib>Bhattarai, Kashi Raj</creatorcontrib><creatorcontrib>Kim, Kyung-Woon</creatorcontrib><creatorcontrib>Soh, Jae-Won</creatorcontrib><creatorcontrib>Kim, Hyung-Ryong</creatorcontrib><creatorcontrib>Chae, Han-Jung</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Junjappa, Raghu Patil</au><au>Kim, Hyun-Kyoung</au><au>Park, Seong Yeol</au><au>Bhattarai, Kashi Raj</au><au>Kim, Kyung-Woon</au><au>Soh, Jae-Won</au><au>Kim, Hyung-Ryong</au><au>Chae, Han-Jung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2019-07-11</date><risdate>2019</risdate><volume>11</volume><issue>7</issue><spage>974</spage><pages>974-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (-133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31336725</pmid><doi>10.3390/cancers11070974</doi><orcidid>https://orcid.org/0000-0003-4190-9889</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Apoptosis Bax protein Binding sites Breast cancer Cancer Cell death Cloning Gene expression Gene regulation Genomes Immunohistochemistry Liver cancer Metastases Mutation Nuclear transport Physiology Polymerase chain reaction Prostate Prostate cancer Protein kinase C Reporter gene siRNA Sp1 protein Transcription factors |
| title | Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC |
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