The ASXL1 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 human hepatic adenocarcinoma cell line. These cells harbor a targeted disruption of the ASXL1 gene, providing a loss-of-function model to study ASXL1-dependent processes. The polyclonal format offers a heterogeneous knockout pool, reflecting the stochastic nature of CRISPR/Cas9-mediated gene editing without clonal selection. This product is suitable for elucidating the functional consequences of ASXL1 deficiency in a liver cancer context.
SK-HEP-1 is a widely used human hepatic adenocarcinoma cell line originally derived from the ascites of a patient with liver adenocarcinoma. Despite its hepatic origin, SK-HEP-1 cells display endothelial-like characteristics, making them a versatile model for studying liver cancer biology, metastasis, and tumor microenvironment interactions. The cell line retains many features of aggressive liver cancer and is amenable to standard culture conditions, facilitating reproducible experimental workflows.
ASXL1 encodes a chromatin-binding protein that functions as a scaffold for polycomb repressive complexes. It physically interacts with BAP1 to form a deubiquitinase module that removes ubiquitin from histone H2A, while also recruiting the PRC2 components EZH2, SUZ12, and EED to catalyze histone H3K27 trimethylation. Through these activities, ASXL1 represses transcription of key target genes including HOXA cluster genes, CDKN2A, and MYC. ASXL1 operates downstream of NOTCH1 signaling and retinoic acid receptor pathways, integrating cellular signals to control myeloid differentiation and maintain genomic stability. Its loss disrupts these epigenetic silencing mechanisms, leading to aberrant gene activation and oncogenic transformation.
In liver cancer, ASXL1 inactivation may contribute to hepatocellular carcinoma progression by dysregulating epigenetic landscapes and promoting proliferation while hindering differentiation. Although ASXL1 mutations are more commonly associated with myeloid malignancies like myelodysplastic syndromes and acute myeloid leukemia, alterations in ASXL1 are also observed in clonal hematopoiesis and solid tumors. This polyclonal knockout model enables dissection of ASXL1’s tumor-suppressive role in hepatic cells, exploration of its cross-talk with Notch and retinoic acid pathways, and assessment of how polycomb repressive complex dysfunction influences liver cancer phenotypes.
This knockout cell population supports functional studies such as ChIP-qPCR for H3K27me3 at target loci, western blotting for histone modifications, and RT-qPCR of HOXA cluster genes and CDKN2A. It is suitable for drug screening with EZH2 inhibitors, co-immunoprecipitation of BAP1, flow cytometry for differentiation markers, proliferation and colony formation assays, and RNA-seq transcriptome profiling. By facilitating mechanistic and pharmacological investigations in a liver cancer context, the ASXL1 Knockout SK-HEP-1 Polyclonal Cells enable diverse epigenetic research. For further information, please contact Ascent Research.
