{"data":{"id":"10.6084/m9.figshare.c.2019779","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2019779","prefix":"10.6084","suffix":"m9.figshare.c.2019779","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Li, Da","givenName":"Da","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Chen, Na-Na","givenName":"Na-Na","familyName":"Chen","affiliation":[],"nameIdentifiers":[]},{"name":"Cao, Ji-Min","givenName":"Ji-Min","familyName":"Cao","affiliation":[],"nameIdentifiers":[]},{"name":"Sun, Wu-Ping","givenName":"Wu-Ping","familyName":"Sun","affiliation":[],"nameIdentifiers":[]},{"name":"Zhou, Yi-Ming","givenName":"Yi-Ming","familyName":"Zhou","affiliation":[],"nameIdentifiers":[]},{"name":"Li, Chun-Yan","givenName":"Chun-Yan","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Xiu-Xia","givenName":"Xiu-Xia","familyName":"Wang","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"BRCA1 as a nicotinamide adenine dinucleotide (NAD)-dependent metabolic switch in ovarian cancer"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Cancer"},{"subject":"Mathematics"},{"subject":"FOS: Mathematics","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Biological Sciences"},{"subject":"Chemistry"},{"subject":"Geology"},{"subject":"FOS: Earth and related environmental sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Pharmacology"},{"subject":"Physiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"Cell Biology"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Both hereditary factors (e.g., BRCA1) and nicotinamide adenine dinucleotide (NAD)-dependent metabolic pathways are implicated in the initiation and progression of ovarian cancer. However, whether crosstalk exists between BRCA1 and NAD metabolism remains largely unknown. Here, we showed that: (i) BRCA1 inactivation events (mutation and promoter methylation) were accompanied by elevated levels of NAD; (ii) the knockdown or overexpression of BRCA1 was an effective way to induce an increase or decrease of nicotinamide phosphoribosyltransferase (Nampt)-related NAD synthesis, respectively; and (iii) BRCA1 expression patterns were inversely correlated with NAD levels in human ovarian cancer specimens. In addition, it is worth noting that: (i) NAD incubation induced increased levels of BRCA1 in a concentration-dependent manner; (ii) Nampt knockdown-mediated reduction in NAD levels was effective at inhibiting BRCA1 expression; and (iii) the overexpression of Nampt led to higher NAD levels and a subsequent increase in BRCA1 levels in primary ovarian cancer cells and A2780, HO-8910 and ES2 ovarian cancer cell lines. These results highlight a novel link between BRCA1 and NAD. Our findings imply that genetic (e.g., BRCA1 inactivation) and NAD-dependent metabolic pathways are jointly involved in the malignant progression of ovarian cancer.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjQvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLkMuMjAxOTc3OTwvaWRlbnRpZmllcj4KICA8Y3JlYXRvcnM+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkRhIExpPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5EYTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5MaTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+TmEtTmEgQ2hlbjwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+TmEtTmE8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+Q2hlbjwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+SmktTWluIENhbzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+SmktTWluPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkNhbzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+V3UtUGluZyBTdW48L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPld1LVBpbmc8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+U3VuPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5ZaS1NaW5nIFpob3U8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPllpLU1pbmc8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+WmhvdTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+Q2h1bi1ZYW4gTGk8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkNodW4tWWFuPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPkxpPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5YaXUtWGlhIFdhbmc8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPlhpdS1YaWE8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+V2FuZzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICA8L2NyZWF0b3JzPgogIDx0aXRsZXM+CiAgICA8dGl0bGU+QlJDQTEgYXMgYSBuaWNvdGluYW1pZGUgYWRlbmluZSBkaW51Y2xlb3RpZGUgKE5BRCktZGVwZW5kZW50IG1ldGFib2xpYyBzd2l0Y2ggaW4gb3ZhcmlhbiBjYW5jZXI8L3RpdGxlPgogIDwvdGl0bGVzPgogIDxkZXNjcmlwdGlvbnM+CiAgICA8ZGVzY3JpcHRpb24gZGVzY3JpcHRpb25UeXBlPSJBYnN0cmFjdCI+Jmx0O2RpdiZndDsmbHQ7cCZndDtCb3RoIGhlcmVkaXRhcnkgZmFjdG9ycyAoZS5nLiwgQlJDQTEpIGFuZCBuaWNvdGluYW1pZGUgYWRlbmluZSBkaW51Y2xlb3RpZGUgKE5BRCktZGVwZW5kZW50IG1ldGFib2xpYyBwYXRod2F5cyBhcmUgaW1wbGljYXRlZCBpbiB0aGUgaW5pdGlhdGlvbiBhbmQgcHJvZ3Jlc3Npb24gb2Ygb3ZhcmlhbiBjYW5jZXIuIEhvd2V2ZXIsIHdoZXRoZXIgY3Jvc3N0YWxrIGV4aXN0cyBiZXR3ZWVuIEJSQ0ExIGFuZCBOQUQgbWV0YWJvbGlzbSByZW1haW5zIGxhcmdlbHkgdW5rbm93bi4gSGVyZSwgd2Ugc2hvd2VkIHRoYXQ6IChpKSBCUkNBMSBpbmFjdGl2YXRpb24gZXZlbnRzIChtdXRhdGlvbiBhbmQgcHJvbW90ZXIgbWV0aHlsYXRpb24pIHdlcmUgYWNjb21wYW5pZWQgYnkgZWxldmF0ZWQgbGV2ZWxzIG9mIE5BRDsgKGlpKSB0aGUga25vY2tkb3duIG9yIG92ZXJleHByZXNzaW9uIG9mIEJSQ0ExIHdhcyBhbiBlZmZlY3RpdmUgd2F5IHRvIGluZHVjZSBhbiBpbmNyZWFzZSBvciBkZWNyZWFzZSBvZiBuaWNvdGluYW1pZGUgcGhvc3Bob3JpYm9zeWx0cmFuc2ZlcmFzZSAoTmFtcHQpLXJlbGF0ZWQgTkFEIHN5bnRoZXNpcywgcmVzcGVjdGl2ZWx5OyBhbmQgKGlpaSkgQlJDQTEgZXhwcmVzc2lvbiBwYXR0ZXJucyB3ZXJlIGludmVyc2VseSBjb3JyZWxhdGVkIHdpdGggTkFEIGxldmVscyBpbiBodW1hbiBvdmFyaWFuIGNhbmNlciBzcGVjaW1lbnMuIEluIGFkZGl0aW9uLCBpdCBpcyB3b3J0aCBub3RpbmcgdGhhdDogKGkpIE5BRCBpbmN1YmF0aW9uIGluZHVjZWQgaW5jcmVhc2VkIGxldmVscyBvZiBCUkNBMSBpbiBhIGNvbmNlbnRyYXRpb24tZGVwZW5kZW50IG1hbm5lcjsgKGlpKSBOYW1wdCBrbm9ja2Rvd24tbWVkaWF0ZWQgcmVkdWN0aW9uIGluIE5BRCBsZXZlbHMgd2FzIGVmZmVjdGl2ZSBhdCBpbmhpYml0aW5nIEJSQ0ExIGV4cHJlc3Npb247IGFuZCAoaWlpKSB0aGUgb3ZlcmV4cHJlc3Npb24gb2YgTmFtcHQgbGVkIHRvIGhpZ2hlciBOQUQgbGV2ZWxzIGFuZCBhIHN1YnNlcXVlbnQgaW5jcmVhc2UgaW4gQlJDQTEgbGV2ZWxzIGluIHByaW1hcnkgb3ZhcmlhbiBjYW5jZXIgY2VsbHMgYW5kIEEyNzgwLCBITy04OTEwIGFuZCBFUzIgb3ZhcmlhbiBjYW5jZXIgY2VsbCBsaW5lcy4gVGhlc2UgcmVzdWx0cyBoaWdobGlnaHQgYSBub3ZlbCBsaW5rIGJldHdlZW4gQlJDQTEgYW5kIE5BRC4gT3VyIGZpbmRpbmdzIGltcGx5IHRoYXQgZ2VuZXRpYyAoZS5nLiwgQlJDQTEgaW5hY3RpdmF0aW9uKSBhbmQgTkFELWRlcGVuZGVudCBtZXRhYm9saWMgcGF0aHdheXMgYXJlIGpvaW50bHkgaW52b2x2ZWQgaW4gdGhlIG1hbGlnbmFudCBwcm9ncmVzc2lvbiBvZiBvdmFyaWFuIGNhbmNlci4mbHQ7L3AmZ3Q7Jmx0Oy9kaXYmZ3Q7PC9kZXNjcmlwdGlvbj4KICA8L2Rlc2NyaXB0aW9ucz4KICA8c3ViamVjdHM+CiAgICA8c3ViamVjdD5DYW5jZXI8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5NYXRoZW1hdGljczwvc3ViamVjdD4KICAgIDxzdWJqZWN0PkJpb2xvZ2ljYWwgU2NpZW5jZXM8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DaGVtaXN0cnk8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5HZW9sb2d5PC9zdWJqZWN0PgogICAgPHN1YmplY3Q+UGhhcm1hY29sb2d5PC9zdWJqZWN0PgogICAgPHN1YmplY3Q+UGh5c2lvbG9neTwvc3ViamVjdD4KICAgIDxzdWJqZWN0Pk1vbGVjdWxhciBCaW9sb2d5PC9zdWJqZWN0PgogICAgPHN1YmplY3Q+R2VuZXRpY3M8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DZWxsIEJpb2xvZ3k8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5CaW9jaGVtaXN0cnk8L3N1YmplY3Q+CiAgPC9zdWJqZWN0cz4KICA8cHVibGlzaGVyPlRheWxvciAmYW1wOyBGcmFuY2lzPC9wdWJsaXNoZXI+CiAgPHB1YmxpY2F0aW9uWWVhcj4yMDE1PC9wdWJsaWNhdGlvblllYXI+CiAgPGRhdGVzPgogICAgPGRhdGUgZGF0ZVR5cGU9IkNyZWF0ZWQiPjIwMTUtMTItMDU8L2RhdGU+CiAgICA8ZGF0ZSBkYXRlVHlwZT0iVXBkYXRlZCI+MjAxOS0wOC0xOTwvZGF0ZT4KICA8L2RhdGVzPgogIDxyZXNvdXJjZVR5cGUgcmVzb3VyY2VUeXBlR2VuZXJhbD0iQ29sbGVjdGlvbiI+Q29sbGVjdGlvbjwvcmVzb3VyY2VU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