The KDM5D Knockout LoVo Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population derived from the LoVo human colorectal adenocarcinoma cell line, engineered for targeted disruption of the KDM5D gene. This loss-of-function model abrogates expression of the histone H3K4me3/me2 demethylase, enabling systematic interrogation of epigenetic regulation and tumor suppression mechanisms. The polyclonal format preserves a heterogeneous pool of edited cells, reflecting inherent genetic variability and making it well-suited for pooled functional assays, including proliferation, invasion, and drug response profiling, without the need for clonal isolation.
The parental LoVo cell line is a widely used metastatic colorectal adenocarcinoma model, originally established from a Dukes’ type C tumor. It exhibits microsatellite stability (MSS) and harbors classical driver mutations in APC, KRAS, and TP53, recapitulating key molecular features of aggressive colorectal cancer. As an epithelial line with robust growth characteristics, LoVo cells serve as a reliable host for investigating oncogenic signaling and drug sensitivity, providing a clinically relevant background for assessing the consequences of KDM5D loss in a defined mutational context.
KDM5D encodes a histone demethylase that specifically removes methyl groups from H3K4me2 and H3K4me3, thereby repressing transcription. It functions downstream of the androgen receptor (AR) and SP1 transcription factor, with its expression modulated by Y chromosome dosage. Mechanistically, KDM5D directly interacts with the retinoblastoma protein (RB1) and the SIN3A-HDAC1/2 co-repressor complex to silence E2F target genes, including CCNA2 and CCNE1, thereby inhibiting cell cycle progression. Furthermore, KDM5D suppresses pro-inflammatory cytokines such as IL-6 and TNF-alpha, and its activity intersects with TGF-beta signaling and RB1-mediated repression of E2F targets, positioning it as a critical regulator of proliferation and immune modulation.
In the LoVo genetic background, already compromised by APC, KRAS, and TP53 mutations, KDM5D knockout is expected to further relieve transcriptional checkpoints, potentially enhancing cell cycling and altering drug sensitivity. The model is particularly relevant for investigating male-specific colorectal cancer biology, given the Y chromosome location of KDM5D. By studying these cells, researchers can dissect how loss of this demethylase impacts RB1-dependent repression and cytokine production, and how such changes influence metastatic behavior and therapeutic response in a well-characterized metastatic colorectal cancer context.
This product supports a broad array of experimental workflows. Expression and epigenetic analyses can be performed via Western blotting, RT-qPCR for targets like CCNA2 and IL-6, and ChIP-qPCR for H3K4me3 modifications. Functional assays include CCK-8 proliferation, flow cytometry for cell cycle and apoptosis (Annexin V/7-AAD), Transwell invasion, and colony formation. Transcriptome-wide effects can be explored by RNA-seq, while drug response profiling can identify synthetic vulnerabilities. The KDM5D Knockout LoVo Polyclonal Cells thus offer a versatile platform for colorectal cancer epigenetic studies, cell cycle regulation, and tumor suppression research. For further technical details or assistance, please contact Ascent Research.
