The KDM5D Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population with targeted disruption of the KDM5D gene in the human SK-HEP-1 liver adenocarcinoma cell line. This heterogeneous pool of edited cells provides a loss-of-function model for studying KDM5D biology without clonal selection bias. Supplied as a ready-to-use polyclonal population, it is optimized for immediate integration into advanced epigenetic and cancer research studies.
SK-HEP-1 cells, originally derived from ascites of a liver adenocarcinoma patient, exhibit a mixed epithelial/mesenchymal phenotype, expressing both epithelial and mesenchymal markers. This characteristic renders them a valuable model for epithelial-mesenchymal transition (EMT), hepatocellular carcinoma (HCC) progression, and metastasis research. The cell line retains relevant signaling pathway aberrations, including those involving p53 and retinoic acid, making it an appropriate host for studying KDM5D function in a hepatic cancer context.
KDM5D encodes a histone lysine demethylase specific for H3K4me2/me3, acting as a transcriptional repressor at target gene promoters. Its activity is regulated by AR, SOX9, retinoic acid, and microRNAs, and it interacts with HDACs, PRC2, RB, and JARID1 family members. KDM5D represses transcription of HOXA9, HOXB13, CDKN1A (p21), and BCL2L11 (BIM), thereby inhibiting proliferation and promoting apoptosis. Knockout abolishes demethylase activity, increasing H3K4me2/me3 at these promoters and activating gene expression, which can enhance cell survival and proliferation. This disruption intersects with p53 and retinoic acid receptor (RAR/RXR) pathways, potentially augmenting tumorigenicity in liver cells.
In SK-HEP-1 cells, KDM5D knockout allows dissection of its dual roles in hepatocellular carcinoma, where it may function as a tumor suppressor or oncogene depending on context. The mixed phenotype facilitates studies of how KDM5D loss impacts EMT and metastatic potential. Eliminating KDM5D-mediated H3K4 demethylation can alter expression of cell cycle, apoptosis, and migration regulators, providing a platform to investigate epigenetic drivers of liver cancer progression and to identify vulnerabilities for therapeutic intervention.
Typical applications include ChIP-qPCR, H3K4me3 ChIP-seq, and RNA-seq to profile epigenetic and transcriptional changes, along with cell proliferation (MTS/CCK-8), migration, and invasion assays to assess functional outcomes. RT-qPCR and Western blotting validate target gene expression, while immunofluorescence visualizes histone mark alterations. This model is ideal for validating histone demethylase inhibitors, exploring KDM5D??s interplay with retinoic acid and p53 signaling, and functional genomics in HCC. For further information, please contact Ascent Research.
