The KDM5B Knockout KYSE-150 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout population for studying the histone demethylase KDM5B in human esophageal squamous cell carcinoma. This heterogeneous pool of KYSE-150 cells with targeted KDM5B disruption enables investigation of its epigenetic regulatory functions without clonal artifacts, providing a robust loss-of-function model in a disease-relevant context.
The parental KYSE-150 cell line was established from a poorly differentiated human esophageal squamous cell carcinoma from a Japanese patient. These epithelial cells are widely used as a model for esophageal cancer biology, including tumorigenesis, metastasis, and drug resistance, and their genetic background suits studies of chromatin-modifying enzymes.
KDM5B is a lysine-specific demethylase 5B that removes di- and tri-methyl groups from histone H3K4 (H3K4me2/3), acting as a transcriptional repressor. It is activated by upstream regulators such as MYC and E2F1 downstream of RB1, and post-transcriptionally controlled by miR-137 and retinoic acid signaling. KDM5B silences tumor suppressors including CDKN1A (p21) and CDKN2A (p16) and HOX genes by demethylating their promoter H3K4me3. It functions within complexes containing HDAC1/2 and the NuRD complex, and interacts with PRC2 components EZH2 and SUZ12 to maintain repressive chromatin. Through the RB-E2F pathway, KDM5B promotes cell cycle progression and stemness while inhibiting epithelial differentiation and EMT. Therefore, its knockout reactivates silenced tumor suppressors, potentially reversing malignancy.
In KYSE-150 esophageal cancer cells, KDM5B disruption provides a model to study how epigenetic silencing drives tumor aggressiveness. KDM5B overexpression correlates with poor prognosis and drug resistance in esophageal squamous cell carcinoma. By abolishing KDM5B, this polyclonal knockout pool allows assessment of cancer cell dependency on KDM5B-mediated repression for proliferation, invasion, and drug survival. The model is valuable for examining re-expression of p21 and p16 and subsequent cell cycle arrest, as well as EMT inhibition, linking chromatin modification to epithelial tumor biology.
These polyclonal knockout cells support functional and pharmacodynamic studies. Researchers can employ Western blotting for H3K4me3, RT-qPCR for CDKN1A, CDKN2A, and HOX transcripts, and ChIP-qPCR for histone marks. Cell-based assays include proliferation, colony formation, migration/invasion, and flow cytometry for cell cycle. RNA-seq enables transcriptomic profiling. Applications encompass epigenetic mechanism studies in esophageal cancer, drug target validation, and inhibitor screening. For further details, contact Ascent Research.
