The KDM5B Knockout NCI-H1703 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human lung squamous cell carcinoma cell line NCI-H1703. This product provides a heterogeneous pool of cells carrying targeted disruptions in the KDM5B gene, enabling loss-of-function studies. The polyclonal format preserves genetic diversity while eliminating the need for single-cell clonal selection, making it suitable for population-level analyses of gene function. The knockout was generated via CRISPR/Cas9-mediated gene disruption, resulting in a KDM5B-deficient model that facilitates investigation of histone demethylase activity and its role in cancer biology.
The parental NCI-H1703 cell line was established from a lung squamous cell carcinoma of a male patient and exhibits adherent epithelial morphology. As a widely employed non-small cell lung cancer (NSCLC) model, NCI-H1703 cells are instrumental in studying tumorigenesis, metastatic progression, and therapeutic responses. The cell line harbors genetic features representative of squamous cell carcinoma of the lung, and its use in conjunction with KDM5B knockout enables dissection of epigenetic mechanisms underlying lung cancer pathogenesis.
KDM5B (JARID1B) encodes a histone H3 lysine 4 demethylase that specifically removes di- and trimethyl groups from H3K4 (H3K4me2/me3), thereby acting as a transcriptional repressor. KDM5B is upregulated by c-MYC, TGF-??, and HIF1A signaling and operates within multi-protein complexes that include RB1, HDAC1, HDAC2, EZH2, SUZ12, MYC, and SMAD3. Through its demethylase activity, KDM5B silences tumor suppressor loci such as CDKN1A (p21), CDKN1B (p27), BAX, and CDH1 (E-cadherin), while also modulating E2F1 target genes. The protein interfaces with H3K4 methyltransferases (e.g., MLL1), HDACs, and the TGF-?? receptor/SMAD3 axis to coordinate chromatin remodeling and transcriptional control. This network positions KDM5B at the intersection of histone demethylation, cell cycle regulation (RB/E2F), and TGF-?? signaling, with context-dependent roles in proliferation, apoptosis, differentiation, and stemness.
Knockout of KDM5B in NCI-H1703 cells is predicted to increase global H3K4 methylation, leading to derepression of KDM5B target genes. Specifically, loss of KDM5B demethylase activity can reactivate expression of CDKN1A and BAX, which encode key regulators of cell cycle arrest and apoptosis, respectively. This epigenetic reprogramming may attenuate oncogenic phenotypes such as unchecked proliferation and survival, providing a mechanistic framework to explore KDM5B??s role in lung squamous cell carcinoma maintenance. The model is particularly valuable for studying the interplay between histone modifications and tumor suppressor gene silencing in NSCLC, and for evaluating the dependency of cancer cells on KDM5B-mediated transcriptional repression.
Researchers can employ this knockout model in a wide array of assays, including Western blotting, RT-qPCR, RNA-seq, and ChIP-qPCR to assess histone methylation marks and gene expression changes; proliferation and migration assays to evaluate phenotypic consequences; and drug sensitivity testing for histone demethylase inhibitor screening. Immunofluorescence and flow cytometry enable single-cell analysis of target protein expression, while luciferase reporter assays can quantify transcriptional activities influenced by KDM5B. The polyclonal population is well-suited for studying tumor suppressor reactivation, EMT, and epigenetic mechanisms of drug resistance in lung cancer. For additional product details or technical support, please contact Ascent Research.
