NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells
NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival ha...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2015-06, Vol.461 (3), p.501-506 |
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| container_title | Biochemical and biophysical research communications |
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| creator | Shoji, Wataru Suenaga, Yusuke Kaneko, Yoshiki Islam, S.M. Rafiqul Alagu, Jennifer Yokoi, Sana Nio, Masaki Nakagawara, Akira |
| description | NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.
•NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro.•NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells.•NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase. |
| doi_str_mv | 10.1016/j.bbrc.2015.04.050 |
| format | Article |
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•NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro.•NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells.•NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2015.04.050</identifier><identifier>PMID: 25896758</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; APOPTOSIS ; Calpain ; CELL CYCLE ; Cell Division ; Cell Line, Tumor ; CELL PROLIFERATION ; CLEAVAGE ; G2 Phase ; GENES ; Genes, myc ; HUMAN POPULATIONS ; Humans ; In Situ Nick-End Labeling ; IN VITRO ; IN VIVO ; Myc-nick ; MYCN ; N-Myc Proto-Oncogene Protein ; NCYM ; Neuroblastoma ; Neuroblastoma - genetics ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Nuclear Proteins - genetics ; Oncogene Proteins - genetics ; PROTEINS ; Real-Time Polymerase Chain Reaction</subject><ispartof>Biochemical and biophysical research communications, 2015-06, Vol.461 (3), p.501-506</ispartof><rights>2015 The Authors</rights><rights>Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-25ab2a3ecac3885616b8f5f0324bbec6fac0e0b444046883c6c9812af20753d83</citedby><cites>FETCH-LOGICAL-c527t-25ab2a3ecac3885616b8f5f0324bbec6fac0e0b444046883c6c9812af20753d83</cites><orcidid>0000-0001-6902-5386</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X15007299$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25896758$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22462069$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Shoji, Wataru</creatorcontrib><creatorcontrib>Suenaga, Yusuke</creatorcontrib><creatorcontrib>Kaneko, Yoshiki</creatorcontrib><creatorcontrib>Islam, S.M. Rafiqul</creatorcontrib><creatorcontrib>Alagu, Jennifer</creatorcontrib><creatorcontrib>Yokoi, Sana</creatorcontrib><creatorcontrib>Nio, Masaki</creatorcontrib><creatorcontrib>Nakagawara, Akira</creatorcontrib><title>NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.
•NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro.•NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells.•NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>APOPTOSIS</subject><subject>Calpain</subject><subject>CELL CYCLE</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>CELL PROLIFERATION</subject><subject>CLEAVAGE</subject><subject>G2 Phase</subject><subject>GENES</subject><subject>Genes, myc</subject><subject>HUMAN POPULATIONS</subject><subject>Humans</subject><subject>In Situ Nick-End Labeling</subject><subject>IN VITRO</subject><subject>IN VIVO</subject><subject>Myc-nick</subject><subject>MYCN</subject><subject>N-Myc Proto-Oncogene Protein</subject><subject>NCYM</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - genetics</subject><subject>Neuroblastoma - metabolism</subject><subject>Neuroblastoma - pathology</subject><subject>Nuclear Proteins - genetics</subject><subject>Oncogene Proteins - genetics</subject><subject>PROTEINS</subject><subject>Real-Time Polymerase Chain Reaction</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT2P1DAQhi0E4paDP0CBItHQJIwd23EkGrTiS7o9GpC4BsueODovib3YCdL9exztQQnVNM-8mnceQp5TaChQ-frYWJuwYUBFA7wBAQ_IjkIPNaPAH5IdAMia9fTbBXmS8xGAUi77x-SCCdXLTqgd-X69vzlUpxTnuLhcoZlOxod6doM3ixuqwx3WweOPDRlWXHwMlQ_V7TqbUB1u9te1mU-TH31hg1tTtJPJS5xNhW6a8lPyaDRTds_u5yX5-v7dl_3H-urzh0_7t1c1CtYtNRPGMtM6NNgqJSSVVo1ihJZxax3K0SA4sJxz4FKpFiX2ijIzMuhEO6j2krw858a8eJ3RLw5vMYbgcNGMcclA9oV6daZKmZ-ry4uefd7uNMHFNWvatUxRaHv6f1Qq2lMQ3YayM4op5pzcqE_JzybdaQp6E6WPehOlN1EauC6iytKL-_zVlmf_XfljpgBvzoArb_vlXdpauYBFTNpKDdH_K_83hfKjHA</recordid><startdate>20150605</startdate><enddate>20150605</enddate><creator>Shoji, Wataru</creator><creator>Suenaga, Yusuke</creator><creator>Kaneko, Yoshiki</creator><creator>Islam, S.M. Rafiqul</creator><creator>Alagu, Jennifer</creator><creator>Yokoi, Sana</creator><creator>Nio, Masaki</creator><creator>Nakagawara, Akira</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7QP</scope><scope>7TK</scope><scope>OTOTI</scope><orcidid>https://orcid.org/0000-0001-6902-5386</orcidid></search><sort><creationdate>20150605</creationdate><title>NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells</title><author>Shoji, Wataru ; Suenaga, Yusuke ; Kaneko, Yoshiki ; Islam, S.M. Rafiqul ; Alagu, Jennifer ; Yokoi, Sana ; Nio, Masaki ; Nakagawara, Akira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-25ab2a3ecac3885616b8f5f0324bbec6fac0e0b444046883c6c9812af20753d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>APOPTOSIS</topic><topic>Calpain</topic><topic>CELL CYCLE</topic><topic>Cell Division</topic><topic>Cell Line, Tumor</topic><topic>CELL PROLIFERATION</topic><topic>CLEAVAGE</topic><topic>G2 Phase</topic><topic>GENES</topic><topic>Genes, myc</topic><topic>HUMAN POPULATIONS</topic><topic>Humans</topic><topic>In Situ Nick-End Labeling</topic><topic>IN VITRO</topic><topic>IN VIVO</topic><topic>Myc-nick</topic><topic>MYCN</topic><topic>N-Myc Proto-Oncogene Protein</topic><topic>NCYM</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma - genetics</topic><topic>Neuroblastoma - metabolism</topic><topic>Neuroblastoma - pathology</topic><topic>Nuclear Proteins - genetics</topic><topic>Oncogene Proteins - genetics</topic><topic>PROTEINS</topic><topic>Real-Time Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shoji, Wataru</creatorcontrib><creatorcontrib>Suenaga, Yusuke</creatorcontrib><creatorcontrib>Kaneko, Yoshiki</creatorcontrib><creatorcontrib>Islam, S.M. Rafiqul</creatorcontrib><creatorcontrib>Alagu, Jennifer</creatorcontrib><creatorcontrib>Yokoi, Sana</creatorcontrib><creatorcontrib>Nio, Masaki</creatorcontrib><creatorcontrib>Nakagawara, Akira</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences 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>Shoji, Wataru</au><au>Suenaga, Yusuke</au><au>Kaneko, Yoshiki</au><au>Islam, S.M. Rafiqul</au><au>Alagu, Jennifer</au><au>Yokoi, Sana</au><au>Nio, Masaki</au><au>Nakagawara, Akira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2015-06-05</date><risdate>2015</risdate><volume>461</volume><issue>3</issue><spage>501</spage><epage>506</epage><pages>501-506</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.
•NCYM promotes cleavages of MYC and MYCN to produce Myc-nick in vitro.•NCYM increases Myc-nick production in MYCN-amplified neuroblastoma cells.•NCYM knockdown decreases Myc-nick production and induces apoptosis at G2/M phase.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25896758</pmid><doi>10.1016/j.bbrc.2015.04.050</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-6902-5386</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES APOPTOSIS Calpain CELL CYCLE Cell Division Cell Line, Tumor CELL PROLIFERATION CLEAVAGE G2 Phase GENES Genes, myc HUMAN POPULATIONS Humans In Situ Nick-End Labeling IN VITRO IN VIVO Myc-nick MYCN N-Myc Proto-Oncogene Protein NCYM Neuroblastoma Neuroblastoma - genetics Neuroblastoma - metabolism Neuroblastoma - pathology Nuclear Proteins - genetics Oncogene Proteins - genetics PROTEINS Real-Time Polymerase Chain Reaction |
| title | NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells |
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