Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway
The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequentl...
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Veröffentlicht in: | Biochemical and biophysical research communications 2016-06, Vol.474 (4), p.660-666 |
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description | The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.
•Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth.•Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.•ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway. |
doi_str_mv | 10.1016/j.bbrc.2016.04.146 |
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•Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth.•Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.•ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2016.04.146</identifier><identifier>PMID: 27150632</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; APOPTOSIS ; BIOLOGICAL MARKERS ; Biomarkers, Tumor - genetics ; BONE MARROW ; CELL PROLIFERATION ; DIAGNOSIS ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic - genetics ; GENE REGULATION ; Genes, Tumor Suppressor ; Genetic Markers - genetics ; Humans ; METHYLATION ; Multiple myeloma ; Multiple Myeloma - genetics ; NEOPLASMS ; Nuclear Proteins - genetics ; PROMOTERS ; PROTEINS ; SKELETON ; THERAPY ; Transcriptional Activation - genetics ; Tumor suppressor ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Proteins - genetics ; ZNF545</subject><ispartof>Biochemical and biophysical research communications, 2016-06, Vol.474 (4), p.660-666</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-b42f0413714b6ef72bca023a3ff1d339034869aeede7fce00acd1094b2df5c8f3</citedby><cites>FETCH-LOGICAL-c417t-b42f0413714b6ef72bca023a3ff1d339034869aeede7fce00acd1094b2df5c8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2016.04.146$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27150632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22598765$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Yu</creatorcontrib><creatorcontrib>Zhan, Qian</creatorcontrib><creatorcontrib>Xu, Hongying</creatorcontrib><creatorcontrib>Li, Lili</creatorcontrib><creatorcontrib>Li, Chen</creatorcontrib><creatorcontrib>Xiao, Qian</creatorcontrib><creatorcontrib>Xiang, Shili</creatorcontrib><creatorcontrib>Hui, Tianli</creatorcontrib><creatorcontrib>Xiang, Tingxiu</creatorcontrib><creatorcontrib>Ren, Guosheng</creatorcontrib><title>Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.
•Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth.•Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.•ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>APOPTOSIS</subject><subject>BIOLOGICAL MARKERS</subject><subject>Biomarkers, Tumor - genetics</subject><subject>BONE MARROW</subject><subject>CELL PROLIFERATION</subject><subject>DIAGNOSIS</subject><subject>Epigenesis, Genetic</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>GENE REGULATION</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic Markers - genetics</subject><subject>Humans</subject><subject>METHYLATION</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>NEOPLASMS</subject><subject>Nuclear Proteins - genetics</subject><subject>PROMOTERS</subject><subject>PROTEINS</subject><subject>SKELETON</subject><subject>THERAPY</subject><subject>Transcriptional Activation - genetics</subject><subject>Tumor suppressor</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>ZNF545</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2LFDEQhoMo7rj6BzxIwIuXHisf3ZkGL7LsqrDoRUG8hHS6MpuhO90m6ZG5-dNNM-se9ZQiPO8DVS8hLxlsGbDm7WHbddFueZm3ILdMNo_IhkELFWcgH5MNADQVb9n3C_IspQMAK0z7lFxwxWpoBN-Q39ez32PA7C31PYbsnbcm-ynQydEfn29qWVOTqKFuCXb9NwPNyzhFmpZ5jphSGX2g4zJkPw9IxxMO02jo0RtqSuL4YJtrQZPfF4MPezqbfPfLnJ6TJ84MCV_cv5fk283116uP1e2XD5-u3t9WVjKVq05yB5IJxWTXoFO8swa4MMI51gvRgpC7pjWIPSpnEcDYvpxCdrx3td05cUlen71Tyl4n6zPaOzuFgDZrzut2p5q6UG_O1BynnwumrEefLA6DCTgtSbOdUIIpodT_UdVCy2XNeEH5GbVxSimi03P0o4knzUCvVeqDXqvUa5UapC41ldCre__Sjdg_RP52V4B3ZwDL2Y4e47oVBou9j-tS_eT_5f8DRMKwbw</recordid><startdate>20160610</startdate><enddate>20160610</enddate><creator>Fan, Yu</creator><creator>Zhan, Qian</creator><creator>Xu, Hongying</creator><creator>Li, Lili</creator><creator>Li, Chen</creator><creator>Xiao, Qian</creator><creator>Xiang, Shili</creator><creator>Hui, Tianli</creator><creator>Xiang, Tingxiu</creator><creator>Ren, Guosheng</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>7TO</scope><scope>H94</scope><scope>OTOTI</scope></search><sort><creationdate>20160610</creationdate><title>Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway</title><author>Fan, Yu ; Zhan, Qian ; Xu, Hongying ; Li, Lili ; Li, Chen ; Xiao, Qian ; Xiang, Shili ; Hui, Tianli ; Xiang, Tingxiu ; Ren, Guosheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-b42f0413714b6ef72bca023a3ff1d339034869aeede7fce00acd1094b2df5c8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>APOPTOSIS</topic><topic>BIOLOGICAL MARKERS</topic><topic>Biomarkers, Tumor - genetics</topic><topic>BONE MARROW</topic><topic>CELL PROLIFERATION</topic><topic>DIAGNOSIS</topic><topic>Epigenesis, Genetic</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>GENE REGULATION</topic><topic>Genes, Tumor Suppressor</topic><topic>Genetic Markers - genetics</topic><topic>Humans</topic><topic>METHYLATION</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>NEOPLASMS</topic><topic>Nuclear Proteins - genetics</topic><topic>PROMOTERS</topic><topic>PROTEINS</topic><topic>SKELETON</topic><topic>THERAPY</topic><topic>Transcriptional Activation - genetics</topic><topic>Tumor suppressor</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>ZNF545</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Yu</creatorcontrib><creatorcontrib>Zhan, Qian</creatorcontrib><creatorcontrib>Xu, Hongying</creatorcontrib><creatorcontrib>Li, Lili</creatorcontrib><creatorcontrib>Li, Chen</creatorcontrib><creatorcontrib>Xiao, Qian</creatorcontrib><creatorcontrib>Xiang, Shili</creatorcontrib><creatorcontrib>Hui, Tianli</creatorcontrib><creatorcontrib>Xiang, Tingxiu</creatorcontrib><creatorcontrib>Ren, Guosheng</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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</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>Fan, Yu</au><au>Zhan, Qian</au><au>Xu, Hongying</au><au>Li, Lili</au><au>Li, Chen</au><au>Xiao, Qian</au><au>Xiang, Shili</au><au>Hui, Tianli</au><au>Xiang, Tingxiu</au><au>Ren, Guosheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2016-06-10</date><risdate>2016</risdate><volume>474</volume><issue>4</issue><spage>660</spage><epage>666</epage><pages>660-666</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The KRAB–zinc-finger protein ZNF545 was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of ZNF545 in tumorigenesis remain unclear. In this study, we investigated the expression and roles of ZNF545 in multiple myeloma (MM). ZNF545 was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues. ZNF545 expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment. ZNF545 methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues. ZNF545 transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of ZNF545 in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified ZNF545 as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of ZNF545 may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.
•Downregulated ZNF545 in MM tissues and cell lines and ectopic expression of ZNF545 suppresses tumor growth.•Tumor-specific methylation of ZNF545 represents an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.•ZNF545 exerts its tumor suppressive effects via transcriptional activating p53 pathway.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27150632</pmid><doi>10.1016/j.bbrc.2016.04.146</doi><tpages>7</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES APOPTOSIS BIOLOGICAL MARKERS Biomarkers, Tumor - genetics BONE MARROW CELL PROLIFERATION DIAGNOSIS Epigenesis, Genetic Gene Expression Regulation, Neoplastic - genetics GENE REGULATION Genes, Tumor Suppressor Genetic Markers - genetics Humans METHYLATION Multiple myeloma Multiple Myeloma - genetics NEOPLASMS Nuclear Proteins - genetics PROMOTERS PROTEINS SKELETON THERAPY Transcriptional Activation - genetics Tumor suppressor Tumor Suppressor Protein p53 - genetics Tumor Suppressor Proteins - genetics ZNF545 |
title | Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway |
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