The HDAC8 Knockout 786-O Polyclonal Cells product provides a ready-to-use CRISPR/Cas9-edited polyclonal cell population derived from the human 786-O clear cell renal cell carcinoma line. Targeted disruption of the HDAC8 gene results in loss of protein function across the pool, and the polyclonal format preserves genetic heterogeneity, enabling robust functional genomic analyses.
The 786-O cell line originates from a primary human renal cell adenocarcinoma and is a standard model of clear cell renal cell carcinoma (ccRCC). It harbors a naturally occurring mutation in the VHL tumor suppressor gene, resulting in constitutive activation of hypoxia-inducible factor (HIF) signaling, a critical driver of ccRCC pathogenesis. These cells display aggressive epithelial morphology and are widely employed for investigating mechanisms of renal carcinogenesis, tumor progression, and drug resistance.
HDAC8 is a class I histone deacetylase that catalyzes the removal of acetyl groups from lysine residues on histone and non-histone substrates. Its deacetylation activity promotes chromatin condensation and generally represses transcription. Key targets include acetylated histone H3 and H4, the microtubule subunit ??-tubulin, the tumor suppressor p53, and the cohesin component SMC3. HDAC8 is regulated upstream by transcription factors such as MYC, E2F1, and TP53, and physically interacts with SMC3, RAD21, NCOR1, HDAC3, ERR??, and ??-tubulin. Through deacetylation of p53, HDAC8 attenuates p53-mediated transcription and apoptosis; deacetylation of SMC3 is essential for cohesin recycling and proper chromosome segregation during mitosis. Consequently, HDAC8 influences cell cycle progression, cytoskeletal dynamics, and chromatin architecture.
In renal cell carcinoma, HDAC8 is frequently overexpressed and associated with poor clinical outcome, as its deacetylase activity drives proliferation and survival. Within the VHL-mutant 786-O context, HDAC8 knockout disrupts these oncogenic programs: loss of HDAC8 leads to hyperacetylation of p53, reactivating its tumor-suppressive functions, and increased SMC3 acetylation, which impairs cohesin recycling and may cause chromosomal instability and mitotic catastrophe. This polyclonal knockout model thus allows investigation of HDAC8-dependent mechanisms in ccRCC, including crosstalk between epigenetic modifications, cell cycle control, and apoptosis, and provides a platform for testing HDAC8-targeted therapies.
This polyclonal HDAC8 knockout cell pool supports diverse applications, including proliferation/apoptosis, migration/invasion, and co-immunoprecipitation assays to study protein interactions. It is suitable for HDAC8 inhibitor screening and drug sensitivity testing. High-throughput methods like RNA-seq and acetyl-proteomics can profile expression and acetylation changes. For validation, western blotting, RT-qPCR, and flow cytometry are recommended. The polyclonal format provides robust population-level results. For additional information, contact Ascent Research.
