{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:43:50Z","timestamp":1788273830735,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019711","name":"London Health Sciences Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multicellular cancer cell aggregates, termed spheroids, are anoikis-resistant, avascular, heterogeneous structures responsible for transcoelomic metastasis of ovarian clear cell carcinoma (OCCC). OCCC is a rare subtype of ovarian cancer with high ARID1A gene mutation rates, resulting in genome-wide changes to H3K27Ac levels and histone deacetylase (HDAC) function. Our study investigated the utility of HDAC inhibitor (HDACi) treatment and H3K27Ac dynamics in OCCC spheroids. By comparing KOC-7c and 105C OCCC cell lines, which have opposing abilities to proliferate as spheroids, we revealed that KOC-7c and 105C spheroids differentially regulated H3K27Ac levels, which correlated with the sensitivity of KOC-7c and the resistance of 105C spheroids to H3K27Ac-altering HDACi treatment. RNA-seq of Entinostat-treated versus vehicle-treated spheroids resulted in a dramatic change in the 105C spheroid transcriptome such that it more closely resembled the proliferative KOC-7c transcriptome over the short term. Comparative pathway analysis identified preferential de-repression of a G2\/M checkpoint gene program in 105C spheroids upon Entinostat treatment when compared directly to the KOC-7c spheroids. Our results suggest that the utility of HDACi in OCCC is highly context-dependent.<\/jats:p>","DOI":"10.3390\/cells15080673","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T12:01:52Z","timestamp":1775822512000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HDAC Inhibition Induces Transient Phenotypic Inertia in Dormant OCCC Spheroids by Derepression of Cell Cycle Genes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3251-6448","authenticated-orcid":false,"given":"Sylvia","family":"Cheng","sequence":"first","affiliation":[{"name":"Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada"},{"name":"Department of Biochemistry, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-5858","authenticated-orcid":false,"given":"Bart","family":"Kolendowski","sequence":"additional","affiliation":[{"name":"Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada"},{"name":"London Health Sciences Centre Research Institute, London, ON N6A 4L6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudith","family":"Ramos-Valdes","sequence":"additional","affiliation":[{"name":"Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada"},{"name":"London Health Sciences Centre Research Institute, London, ON N6A 4L6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-8066","authenticated-orcid":false,"given":"Trevor G.","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada"},{"name":"London Health Sciences Centre Research Institute, London, ON N6A 4L6, Canada"},{"name":"Department of Oncology, Western University, London, ON N6A 3K7, Canada"},{"name":"Department of Anatomy & Cell Biology, Western University, London, ON N6A 3K7, Canada"},{"name":"Department of Obstetrics & Gynaecology, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2796-9941","authenticated-orcid":false,"given":"Gabriel E.","family":"DiMattia","sequence":"additional","affiliation":[{"name":"Mary & John Knight Translational Ovarian Cancer Research Unit, Verspeeten Family Cancer Centre, London, ON N6A 4L6, Canada"},{"name":"Department of Biochemistry, Western University, London, ON N6A 3K7, Canada"},{"name":"London Health Sciences Centre Research Institute, London, ON N6A 4L6, Canada"},{"name":"Department of Oncology, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1101\/gad.351444.123","article-title":"Epigenetic Modulators Provide a Path to Understanding Disease and Therapeutic Opportunity","volume":"38","author":"Honer","year":"2024","journal-title":"Genes Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/bs.ircmb.2024.03.006","article-title":"Epigenetic Regulation in Ovarian Cancer","volume":"387","author":"Thi","year":"2024","journal-title":"Int. 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