The BRCC3 Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population carrying targeted disruptions of the BRCC3 gene in the SK-HEP-1 human hepatocellular carcinoma line. This loss-of-function model enables systematic investigation of BRCC3-dependent mechanisms in an epithelial cancer background. The heterogeneous editing pattern of polyclonal cells provides a robust platform for functional genomic studies without clonal selection bias.
SK-HEP-1 is a liver adenocarcinoma cell line originally derived from the ascites of a hepatocellular carcinoma patient. This widely used model retains key oncogenic features, including dysregulated DNA repair and signaling pathways, making it appropriate for examining the consequences of BRCC3 ablation within the hepatic microenvironment.
BRCC3 encodes a K63-specific deubiquitinase that assembles into two mutually exclusive complexes. In the BRCA1-A complex, alongside ABRAXAS1, BRCA1, RAP80, and MERIT40, BRCC3 is recruited by RNF8/RNF168 downstream of ATM/ATR signaling to restrict DNA end resection and promote non-homologous end joining. Within the BRISC complex, with ABRO1 and CCDC98, BRCC3 deubiquitinates NLRP3 to facilitate inflammasome activation and IL-1?? secretion, and targets STAT1 to modulate type I interferon responses via IRF9. These activities are influenced by upstream cytokines such as TNF-?? and IL-1?? and converge on downstream NF-??B and interferon pathways.
In hepatocellular carcinoma, disruption of BRCC3 shifts DNA repair pathway choice, impacting sensitivity to cisplatin and olaparib. Concurrently, impaired deubiquitination of NLRP3 and STAT1 alters inflammatory and interferon responses, which are relevant to tumor progression and immune evasion. The SK-HEP-1 background thus enables study of the dual roles of BRCC3 in genome maintenance and innate immunity.
This product is suitable for a range of assays, including ??H2AX immunofluorescence for DNA damage foci, comet assays for DNA strand breaks, NF-??B luciferase reporter assays, and NLRP3 inflammasome activation measured by IL-1?? secretion. Downstream target expression (e.g., NLRP3, STAT1, SMC1A) can be monitored by RT-qPCR and western blot, while drug sensitivity screens address therapeutic responses. Together, these tools enable comprehensive analysis of ubiquitin signaling, DNA repair, and immune pathways in liver cancer research. For additional information, please contact Ascent Research.
