The HDAC8 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-mediated gene-disrupted cell population engineered from the UM-UC-3 human bladder carcinoma cell line. This polyclonal knockout model generates a heterogeneous loss-of-function system to interrogate the biological functions of histone deacetylase 8 (HDAC8). The product provides a versatile tool for dissecting HDAC8-dependent signaling in an aggressive bladder cancer context, offering a relevant genetic background for comparative functional studies against parental UM-UC-3 cells.
UM-UC-3 is an extensively characterized epithelial cell line derived from a grade III, invasive urinary bladder transitional cell carcinoma obtained from a male patient. This cell line recapitulates key features of high-grade urothelial carcinoma and is widely employed to investigate bladder cancer biology, including oncogenic signaling pathways, drug responses, and metastatic behavior. Its aggressive phenotype and well-documented molecular profile make it particularly suitable for evaluating the impact of HDAC8 disruption on tumorigenic processes.
HDAC8 is a class I histone deacetylase that catalyzes the removal of acetyl groups from lysine residues on histones and non-histone proteins. It deacetylates histone H3 at K9 and K14 and H4 at K16, leading to chromatin condensation and transcriptional repression. Beyond histones, HDAC8 deacetylates p53 at lysine 382, inhibiting p53 transcriptional activity and suppressing expression of cell cycle inhibitor p21/WAF1 and pro-apoptotic BAX. Moreover, HDAC8 deacetylates the cohesin subunit SMC3, regulating sister chromatid cohesion. Its activity is modulated by upstream signals including retinoic acid, MYC transcription factor, cAMP/PKA pathway, and CK2 kinase. HDAC8 interacts with the N-CoR/SMRT co-repressor complex, protein phosphatase 1, and HSP70, integrating into broader regulatory networks.
In UM-UC-3 bladder cancer cells, CRISPR/Cas9-mediated disruption of HDAC8 leads to hyperacetylation of its substrates, thereby relieving transcriptional repression of tumor-suppressive genes and impairing sister chromatid cohesion. This knockout model enables researchers to investigate HDAC8 dependency in high-grade urothelial carcinoma, dissect mechanisms of resistance to HDAC inhibitors, and assess the functional consequences of cohesin deregulation. The polyclonal nature preserves genetic heterogeneity, closely mirroring the complexity of tumor cell populations and facilitating robust phenotypic analyses.
This product supports a wide range of experimental applications, including Western blotting for acetylated histones (e.g., Ac-H3K9, Ac-H4K16) and p53 acetylation, RT-qPCR for downstream targets such as p21 and BAX, flow cytometry for cell cycle and apoptosis assays, ChIP-qPCR for histone acetylation at specific promoters, and immunofluorescence to visualize sister chromatid cohesion defects. Additionally, it is suitable for drug sensitivity assays with HDAC inhibitors, colony formation, and migration/invasion studies. For further details and technical support, please contact Ascent Research.
