This product is a CRISPR/Cas9-edited polyclonal knockout cell population targeting the KDM1A gene in the human SK-HEP-1 hepatocellular carcinoma cell line. The polyclonal format provides a heterogeneous pool of cells harboring targeted gene disruptions, enabling the study of KDM1A loss of function without clonal selection biases. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, generating a versatile loss-of-function model suitable for investigating KDM1A-dependent cellular processes.
The SK-HEP-1 host cell line is derived from the ascites of a patient with liver adenocarcinoma and represents malignant liver epithelial cells. This cell line is widely used as a model for human hepatocellular carcinoma, exhibiting key features of hepatic tumor biology including uncontrolled proliferation, migratory capacity, and altered metabolic profiles. Its epithelial origin and tumorigenic properties make it a relevant platform for dissecting mechanisms driving liver cancer progression and for evaluating potential therapeutic interventions.
KDM1A (LSD1) is a flavin-dependent histone demethylase that specifically removes mono- and dimethyl groups from lysine 4 and lysine 9 of histone H3 (H3K4me1/2 and H3K9me1/2), thereby functioning as a transcriptional corepressor or coactivator depending on context. KDM1A operates within multiple signaling axes: it is regulated by upstream factors such as androgen receptor (AR), estrogen receptor (ER), MYCN, REST, TGF??, hypoxia, and EGF, and it transcriptionally controls downstream targets including CDH1 (E-cadherin), CDH2 (N-cadherin), SNAI1, VEGFA, CCND1, TP53, HNF4A, and TERT. Mechanistically, KDM1A forms complexes with corepressors like RCOR1, HDAC1, HDAC2, and components of the NuRD complex, and it interacts with transcription factors such as SNAI1 and GFI1 to modulate gene expression programs. Through these interactions, KDM1A integrates signals from AR and ER pathways, TGF??/Smad, Notch, and Wnt/??-catenin cascades, thereby orchestrating epigenetic remodeling that promotes oncogenesis and epithelial-mesenchymal transition (EMT).
In the context of hepatocellular carcinoma, KDM1A plays a critical role in tumor progression by silencing tumor suppressor genes such as CDH1 and activating oncogenic networks that facilitate EMT and cancer stem cell maintenance. The demethylation of H3K4me2 by KDM1A at promoter regions of target genes leads to transcriptional repression of epithelial markers and activation of mesenchymal and pro-angiogenic factors like VEGFA. Consequently, KDM1A knockout in SK-HEP-1 cells is expected to relieve this repression, providing a powerful model to investigate the epigenetic mechanisms underlying liver cancer aggressiveness and to assess the functional consequences of KDM1A ablation on cell behavior, signaling, and chromatin states.
This KDM1A knockout polyclonal SK-HEP-1 cell population is suited for a broad range of research applications, including hepatocellular carcinoma pathophysiology, epigenetic therapy development, CRISPR-based knockout phenotyping, EMT mechanistic studies, and cancer stem cell biology. Researchers can employ representative technical assays such as Western blotting and RT-qPCR to confirm knockout and downstream target changes, ChIP-qPCR to assess H3K4me2 enrichment at specific loci, immunofluorescence and flow cytometry for protein expression and phenotype analysis, and functional assays including cell proliferation, Transwell migration/invasion, and colony formation. Transcriptional profiling by RNA-seq and direct measurement of histone demethylase activity further extend the analytical depth. This model serves as a robust tool for dissecting KDM1A-dependent regulatory networks and for screening potential LSD1 inhibitors. For further information, please contact Ascent Research.
