The KDM5C Knockout SK-OV-3 Polyclonal Cells are a CRISPR/Cas9-edited population of the human ovarian adenocarcinoma cell line SK-OV-3, with targeted disruption of the KDM5C gene. This polyclonal pool contains diverse mutations without clonal selection, preserving genetic heterogeneity. The editing process generates a spectrum of indels that disrupt the coding sequence, leading to loss of functional KDM5C protein. This format enables robust functional studies that average out clonal variation and better represent tumor cell diversity.
SK-OV-3 is an epithelial ovarian cancer line derived from the ascites of a 64-year-old female, harboring a homozygous TP53 R175H mutation. Widely used in oncology research, these cells exhibit aggressive proliferation, invasiveness, and drug resistance. The p53-deficient background provides a clinically relevant context for studying epigenetic modifiers, as TP53 mutations often synergize with chromatin dysregulation in ovarian tumorigenesis.
KDM5C demethylates H3K4me2/me3, functioning as a transcriptional repressor within the REST corepressor complex alongside REST, HDAC1/2, CoREST, and LSD1. It targets genes such as SYN1, GRIN2B, and CDKN1A, influencing cell cycle and neuronal silencing. Upstream regulators include MYC and E2F, and it interacts with RB. Its activity counteracts MLL methyltransferase complexes, and dysregulation alters chromatin architecture.
In SK-OV-3 cells, KDM5C knockout likely reshapes the epigenetic landscape, potentially affecting proliferation, migration, and invasion. Loss of KDM5C may derepress REST target genes, including neuronal programs or tumor suppressors, in a context-dependent manner. Interaction with RB suggests growth regulatory roles, and disruption in TP53-mutant cells could reveal synthetic lethalities or altered drug responses. This model is valuable for exploring histone demethylase function in ovarian cancer chemoresistance and epigenetics.
Applications include cancer epigenetics, target validation, and chromatin studies. Key assays are RNA-seq and ChIP-seq for transcriptional and histone modification profiling, proliferation assays (MTT/XTT), colony formation, migration/invasion tests, and flow cytometry for cell cycle and apoptosis. Routine validation uses Western blotting and RT-qPCR. This polyclonal knockout pool is also suited for high-throughput drug screening. Contact Ascent Research for further information.
