The KDM6A Knockout SK-HEP-1 Polyclonal Cells product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human liver adenocarcinoma cell line. This loss-of-function model targets the KDM6A gene (also known as UTX), thereby enabling researchers to interrogate the functional consequences of KDM6A disruption in a hepatic epithelial context. The polyclonal population consists of a heterogeneous mix of cells carrying diverse CRISPR-mediated gene disruptions, providing a robust system for assessing gene function without the bottleneck effects of clonal selection.
SK-HEP-1 cells were originally established from the ascitic fluid of a patient with liver adenocarcinoma and exhibit both epithelial and endothelial characteristics. This cell line is widely employed in hepatocellular carcinoma research, hepatocyte biology studies, drug metabolism assays, and liver cancer therapeutic development. Its dual phenotype makes it a valuable platform for dissecting the crosstalk between epithelial and mesenchymal traits, processes closely linked to tumor progression and metastasis.
KDM6A functions as a histone H3 lysine 27 (H3K27) demethylase that removes di- and trimethyl marks (H3K27me2/3), leading to chromatin relaxation and transcriptional activation. It is regulated by upstream signals including retinoic acid, NOTCH1, TGFB1, and TP53, and it physically interacts with components of the MLL3/4 complexes, ASXL1, p53, SMADs, and beta-catenin. KDM6A activates a network of tumor suppressor genes such as CDKN1A (p21), CDKN2A (p16), RB1, TP53, BAX, FAS, and CDH1 (E-cadherin), thereby enforcing cell cycle arrest and apoptosis. Its activity opposes EZH2-mediated H3K27 methylation, thus balancing the repressive and active chromatin states at key developmental and cancer-related loci.
Disruption of KDM6A in SK-HEP-1 cells abolishes its demethylase activity, leading to elevated H3K27me3 levels at promoter regions of its direct targets and consequent transcriptional silencing of tumor suppressors. This epigenetic remodeling mimics oncogenic conditions observed in human liver and other cancers, where KDM6A is frequently mutated or downregulated. The resulting SK-HEP-1 polyclonal knockout model exhibits enhanced proliferative capacity, impaired apoptosis, and altered migratory behavior, providing a physiologically relevant system to study KDM6A-dependent epigenetic dysregulation in liver adenocarcinoma.
Researchers can utilize this knockout cell population to investigate KDM6A??s role in epigenetic regulation of hepatocellular carcinoma, validate downstream pathways through transcriptomic profiling by RNA-seq, or perform chromatin immunoprecipitation (ChIP-qPCR) to map H3K27me3 occupancy changes at specific gene loci. Functional assays for cell proliferation, apoptosis, and migration/invasion enable quantitative assessment of tumorigenic phenotypes, while drug sensitivity screening can identify compounds that exploit synthetic lethality with KDM6A loss. Additionally, these cells serve as a critical tool for dissecting the interplay between KDM6A and major signaling cascades like TGF-beta, Wnt, and Notch. For further details on batch-specific knockout efficiency or technical support, please contact Ascent Research.
