{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:00:27Z","timestamp":1789912827645,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,5,14]],"date-time":"2012-05-14T00:00:00Z","timestamp":1336953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising from the mesothelial cells lining the parietal pleura and it exhibits poor prognosis. Although there has been significant progress in MPM treatment, development of more efficient therapeutic approaches is needed. <jats:italic>BMAL1<\/jats:italic> is a core component of the circadian clock machinery and its constitutive overexpression in MPM has been reported. Here, we demonstrate that <jats:italic>BMAL1<\/jats:italic> may serve as a molecular target for MPM. The majority of MPM cell lines and a subset of MPM clinical specimens expressed higher levels of <jats:italic>BMAL1<\/jats:italic> compared to a nontumorigenic mesothelial cell line (MeT\u20105A) and normal parietal pleural specimens, respectively. A serum shock induced a rhythmical <jats:italic>BMAL1<\/jats:italic> expression change in MeT\u20105A but not in ACC\u2010MESO\u20101, suggesting that the circadian rhythm pathway is deregulated in MPM cells. <jats:italic>BMAL1<\/jats:italic> knockdown suppressed proliferation and anchorage\u2010dependent and independent clonal growth in two MPM cell lines (ACC\u2010MESO\u20101 and H290) but not in MeT\u20105A. Notably, <jats:italic>BMAL1<\/jats:italic> depletion resulted in cell cycle disruption with a substantial increase in apoptotic and polyploidy cell population in association with downregulation of Wee1, cyclin B and p21<jats:sup>WAF1\/CIP1<\/jats:sup> and upregulation of cyclin E expression. <jats:italic>BMAL1<\/jats:italic> knockdown induced mitotic catastrophe as denoted by disruption of cell cycle regulators and induction of drastic morphological changes including micronucleation and multiple nuclei in ACC\u2010MESO\u20101 cells that expressed the highest level of <jats:italic>BMAL1<\/jats:italic>. Taken together, these findings indicate that <jats:italic>BMAL1<\/jats:italic> has a critical role in MPM and could serve as an attractive therapeutic target for MPM.<\/jats:p>","DOI":"10.1002\/ijc.27598","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T12:00:17Z","timestamp":1334664017000},"page":"2820-2831","source":"Crossref","is-referenced-by-count":67,"title":["The circadian clock gene <i>BMAL1<\/i> is a novel therapeutic target for malignant pleural mesothelioma"],"prefix":"10.1002","volume":"131","author":[{"given":"Momen","family":"Elshazley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuo","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsunari","family":"Hase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenya","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Toyokuni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Ishiguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Osada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Sekido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Yokoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyasu","family":"Usami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Shames","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi F.","family":"Gazdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Minna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,14]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67025-0"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12199-007-0015-8"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.8523"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0551"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81199-X"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(07)70373-X"},{"key":"e_1_2_5_8_2","first-page":"7545","article-title":"The days and nights of cancer cells","volume":"63","author":"Canaple L","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00205-1"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1119"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086271"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1072"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2011.1207"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-009-0761-7"},{"key":"e_1_2_5_15_2","first-page":"7277","article-title":"A molecular mechanism regulating circadian expression of vascular endothelial growth factor in tumor cells","volume":"63","author":"Koyanagi S","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006554"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00184.x"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2010.04.008"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.5858\/133.8.1317"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2521"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4199"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705576200"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004798"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0177"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.050"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059542"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00439-09"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1178"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.393"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200703202"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.09.024"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-5521-5"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.27598","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.27598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T15:41:40Z","timestamp":1697470900000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.27598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,14]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12,15]]}},"alternative-id":["10.1002\/ijc.27598"],"URL":"https:\/\/doi.org\/10.1002\/ijc.27598","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,14]]}}}