{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:45Z","timestamp":1786566525033,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vorinostat (suberoylanilide hydroxamic acid, SAHA) is a histone deacetylase (HDAC) class I\/II inhibitor that has been evaluated in clinical trials for efficacy in pediatric cancers. Previous studies demonstrated cellular responses to SAHA in retinoblastoma (RB), a pediatric intraocular cancer. However, its mechanism of action remains incompletely understood. In this report, we demonstrate that SAHA inhibition of cell proliferation and induction of cell death was associated with the downregulation of the FOXM1 oncogene in the MYCN\u2010driven RB1\u2010\/RB1\u2010cell lines WERI\u2010RB1 and Y79, of which Y79 exhibits greater metastatic potential. SAHA also deregulated cell cycle genes that are targeted by FOXM1. Additionally, SAHA inhibited RB metastatic signaling, including inhibiting the expression of MMP2, a transcriptional target of FOXM1. Further, because SAHA inhibition of FOXM1 positively correlated with suppression of the MYCN oncogene, we demonstrated that genomic knockdown of MYCN in the RB cell lines resulted in FOXM1 downregulation. Finally, we showed that FOXM1 inhibition downregulated NF\u2010\u03ba\u03b2 and inhibition of FOXM1 suppressed FOXM1 expression in the RB cell lines. Taken together, these results indicated that SAHA inhibition of FOXM1 oncogenic signaling may be mediated by MYCN in RB. Although the current data provide a preclinical rationale for the consideration of SAHA either as a single agent or in combination with other therapies, for the treatment of metastatic RB with MYCN\u2010amplified RB1\u2010\/RB1\u2010molecular phenotype, further research is warranted to gain greater insight into FOXM1\u2010MYCN interaction in response to SAHA, in this molecular subtype of RB.<\/jats:p>","DOI":"10.1002\/jbt.70834","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:20Z","timestamp":1775807720000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vorinostat Inhibition of FOXM1 Oncogenic Signaling Is Associated With the Downregulation of MYCN Transcription in Metastatic Retinoblastoma"],"prefix":"10.1002","volume":"40","author":[{"given":"Onyekwere","family":"Onwumere","sequence":"first","affiliation":[{"name":"Biology Doctoral Program, The Graduate School and University Center, City University of New York New York New York USA"},{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5156-9051","authenticated-orcid":false,"given":"Anastassiya","family":"Kim","sequence":"additional","affiliation":[{"name":"Biology Doctoral Program, The Graduate School and University Center, City University of New York New York New York USA"},{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sual","family":"Lopez","sequence":"additional","affiliation":[{"name":"Biology Doctoral Program, The Graduate School and University Center, City University of New York New York New York USA"},{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Sauane","sequence":"additional","affiliation":[{"name":"Biology Doctoral Program, The Graduate School and University Center, City University of New York New York New York USA"},{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Yamraj","sequence":"additional","affiliation":[{"name":"The Department of Nursing Utica University Utica New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine Jack and Pearl Resnick Campus, Bronx  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda Saxe","family":"Einbond","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"},{"name":"The New York Botanical Garden, Bronx  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Redenti","sequence":"additional","affiliation":[{"name":"Biology Doctoral Program, The Graduate School and University Center, City University of New York New York New York USA"},{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-3808","authenticated-orcid":false,"given":"Rajendra","family":"Gharbaran","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Lehman College\/City University of New York, Bronx New York USA"},{"name":"Department of Biological Sciences Bronx Community College\/City University of New York, 2155 University Avenue, Bronx  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-1-31"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61137-9"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-017-0050-x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.150292"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13813"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.68.4.820"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70045-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24329"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11020251"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3909"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz160"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27947"},{"key":"e_1_2_10_14_1","first-page":"1292","article-title":"Differential Gene Expression Profile of Retinoblastoma Compared to Normal Retina","volume":"16","author":"Ganguly A.","year":"2010","journal-title":"Molecular Vision"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.623679"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26510"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-401687"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4836"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3517"},{"issue":"1","key":"e_1_2_10_20_1","first-page":"460","article-title":"Histone Deacetylase Inhibitors Differentially Regulate c\u2010Myc Expression in Retinoblastoma Cells","volume":"19","author":"Yu N.","year":"2020","journal-title":"Oncology Letters"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(12)80048-2"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(12)80048-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.15287"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2020.151657"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2012.11.004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155392"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113561"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-019-4241-0"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.34272"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407173-5.00004-2"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19254"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-134"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0640"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3418-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-89"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1506"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.249"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043854"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0040-3"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44435-5"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000134"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.253"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31196"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0226"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.037"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.475"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-024-00989-9"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008522107"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2020.61.1.20"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000585"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3129"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2018.12.018"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2019.1565470"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70834","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70834","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T19:46:27Z","timestamp":1786563987000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jbt.70834"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70834","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2024-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70834"}}