The HDAC8 Knockout HCT 116 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population from the HCT 116 human colorectal carcinoma line. This product features targeted disruption of HDAC8, creating a loss-of-function model for studying histone deacetylase 8 in cancer biology. The polyclonal nature avoids clonal biases while representing the heterogeneous knockout background.
HCT 116 is a well-established colorectal carcinoma model with epithelial morphology, KRAS G13D and CTNNB1 mutations, microsatellite instability (MSI), and a near-diploid karyotype. These features make it suitable for investigating oncogenic signaling, chromosomal instability, and DNA repair defects within a colorectal tumor context.
HDAC8 is a class I histone deacetylase that targets acetylated lysines on histones H3 (H3K27) and H4 (H4K16), as well as non-histone substrates including p53, the cohesin subunit SMC3, and cortactin. Upstream regulators include transcription factors HOXA10, p53, and Sp1, microRNAs miR-216a and miR-129, and IL-6/JAK/STAT signaling. Deacetylation of p53 reduces its transcriptional activity, altering CDKN1A (p21) and BCL2 family expression to control cell cycle and apoptosis. SMC3 deacetylation modulates cohesin complex dynamics for sister chromatid cohesion and gene regulation, while cortactin deacetylation affects actin polymerization and cell migration. HDAC8 interacts with the cohesin complex (SMC1, SMC3, RAD21), the NuRD component MTA1, HDAC3, the SMRT/NCoR corepressor, and transcription factors ERR?? and CREB, linking it to Wnt/??-catenin and EMT programs via regulation of SNAI1 (Snail).
In the HCT 116 context, with KRAS G13D and CTNNB1 mutations and MSI, HDAC8 knockout disrupts deacetylation of histones and substrates, causing hyperacetylation of H3K27, H4K16, p53, and SMC3. This can trigger p53/p21-mediated cell cycle arrest and apoptosis, and impair cohesin-dependent processes. The model is thus valuable for studying HDAC8’s role in colorectal cancer proliferation, genomic stability, and its crosstalk with oncogenic KRAS and ??-catenin. The epithelial origin also permits investigation of HDAC8 in EMT, migration, and metastasis.
Applications include Western blotting for histone and non-histone acetylation, RT-qPCR and RNA-seq for gene expression profiling, ChIP-qPCR for chromatin modifications, and immunofluorescence. Flow cytometry can assess cell cycle and apoptosis, while migration and invasion assays evaluate EMT-related phenotypes. Co-immunoprecipitation studies can map altered HDAC8 interactomes. The cells are suitable for HDAC inhibitor sensitivity screens, combination therapy testing with chemotherapeutics, and as a control in CRISPR rescue experiments. For further information, please contact Ascent Research.
