HDAC inhibition induces transient phenotypic inertia in dormant OCCC spheroids by derepression of cell cycle genes

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 regulate H3K27Ac levels, which correlates 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.