The KDM5C Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the UM-UC-3 urothelial carcinoma line. This loss-of-function model enables study of KDM5C (lysine-specific demethylase 5C) in chromatin remodeling, transcriptional repression, and tumorigenesis. The polyclonal format minimizes clonal variation, ensuring reproducible results in functional genomics and drug screens. Gene disruption is achieved by targeting KDM5C with CRISPR/Cas9, yielding a heterogeneous pool of cells with gene-inactivating lesions; no monoclonality or complete knockout is guaranteed. This population is ideal for initial pathway dissection and high-throughput assays.
UM-UC-3, derived from a male bladder cancer patient, is a TP53-mutant, tumorigenic cell line representing invasive urothelial carcinoma. It is widely used to model bladder cancer, exhibiting adherent epithelial morphology and capabilities for migration, invasion, and xenograft tumor formation. The cell line expresses various histone-modifying enzymes, making it a relevant host for epigenetic studies of urothelial carcinoma progression and drug sensitivity.
KDM5C is a histone H3K4 di-/tri-demethylase that represses transcription by removing methyl marks at gene promoters. It functions within corepressor complexes containing HDAC1/2, REST, SIN3A, and SIN3B, integrating histone deacetylation and demethylation. Upstream regulators include retinoic acid, androgen receptor, and TGF-?? signals. KDM5C directly represses targets such as HOXA genes, CDKN1A (p21), and RB1, thereby influencing cell cycle, differentiation, and genomic stability. Its activity links extracellular signals to chromatin structure and gene expression programs with implications for tumorigenesis.
Knocking out KDM5C in UM-UC-3 cells provides a system to explore its roles in bladder cancer, where altered histone methylation is common. Mutations in KDM5C are associated with X-linked intellectual disability and cancers including bladder and renal cell carcinomas. The polyclonal knockout approach avoids clonal artifacts, better reflecting tumor heterogeneity. This model permits investigation of KDM5C-dependent transcriptional changes and potential cooperation with TP53 deficiency to drive neoplastic behavior.
Applications include western blot, RT-qPCR, and ChIP-qPCR for H3K4me3 to validate KDM5C loss and its effects, along with cell-based assays for proliferation, migration, and invasion. The polyclonal population is well-suited for high-throughput RNA-seq or ATAC-seq to map KDM5C-dependent transcriptomes and chromatin landscapes, and for testing HDAC inhibitor sensitivity. For further information or to discuss customized projects, please contact Ascent Research.
