The CBX8 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of the 786-O human clear cell renal cell carcinoma (ccRCC) line, featuring targeted disruption of the CBX8 gene to create a loss-of-function model. This heterogeneous pool incorporates diverse editing events, avoiding the artifacts of single-cell cloning while enabling robust interrogation of CBX8-dependent biology. The cells are supplied as an actively growing culture, ready for expansion and immediate use in experimental workflows.
786-O cells were originally isolated from a primary renal cell adenocarcinoma of a 58-year-old male and carry a mutation in the VHL tumor suppressor gene, a hallmark of sporadic ccRCC. This adherent epithelial line is widely recognized as a faithful model for studying the molecular pathogenesis of kidney cancer, including constitutive activation of hypoxia-inducible factor pathways and associated epigenetic alterations. Its well-characterized genetics and broad availability make it a cornerstone in renal cancer research.
CBX8 encodes a chromobox protein that functions as a non-catalytic subunit of Polycomb repressive complex 1 (PRC1). It directly binds H3K27me3, the repressive mark written by the PRC2 complex (EZH2 and SUZ12), and interacts with core PRC1 components RING1A/RING1B, BMI1, and PCGF proteins to mediate chromatin compaction and stable transcriptional silencing. CBX8?PRC1 targets include the CDKN2A (p16INK4a) and CDKN2B (p15INK4b) loci, whose products inhibit cyclin-dependent kinases and activate RB, as well as CDKN1A (p21), a key mediator of p53-dependent growth arrest. By repressing these tumor suppressors, CBX8 promotes cell cycle progression and stemness, and its disruption leads to their derepression, induction of senescence, and growth inhibition.
In the context of 786-O renal carcinoma cells, loss of CBX8 provides a unique window into the role of PRC1 in maintaining the malignant phenotype of VHL-deficient ccRCC. The VHL mutation is known to drive epigenetic reprogramming, and CBX8 knockout can expose synthetic lethal interactions or restore expression of silenced tumor suppressors, potentially reversing oncogenic properties. This model is particularly valuable for investigating how Polycomb-mediated gene silencing cooperates with hypoxia signaling pathways to sustain tumor growth, and for evaluating novel epigenetic therapeutic strategies.
Researchers can utilize this polyclonal knockout population in a range of downstream assays, including RT-qPCR and RNA-seq to quantify transcriptomic changes, chromatin immunoprecipitation (ChIP-qPCR) to verify alterations in H3K27me3 or CBX8 occupancy at target genes, and immunoblotting to confirm protein-level effects. Phenotypic analyses such as MTS or colony formation assays measure growth inhibition, while senescence-associated ??-galactosidase staining assesses senescence induction. These cells also facilitate high-throughput screens for small molecules that synergize with CBX8 loss. For further information, contact Ascent Research.
