The INO80C Knockout SK-HEP-1 Polyclonal Cells product provides a CRISPR/Cas9-mediated polyclonal knockout cell population targeting the human INO80C gene in the SK-HEP-1 hepatic adenocarcinoma cell line. This polyclonal population comprises a heterogeneous mixture of edited cells with disruption of the INO80C locus, offering a loss-of-function model system that avoids the clonal selection biases inherent in single-cell-derived lines. The knockout product is designed to generate reproducible inactivation of INO80C, enabling investigation of its cellular roles without presupposing a specific editing outcome. Researchers can employ these cells to dissect INO80C-dependent phenotypes in a near-native tumor cell background, facilitating robust functional genomics and pathway analysis.
The parental SK-HEP-1 line was originally derived from the ascites of a patient with liver adenocarcinoma and exhibits an adherent epithelial morphology with wild-type p53 status. These cells are widely established as a hepatocellular carcinoma (HCC) model for studying hepatic tumor biology, including metastatic behavior, metabolic reprogramming, and drug response. Their epithelial origin and tumorigenic properties render them particularly relevant for probing the molecular underpinnings of liver cancer. The retention of a functional p53 pathway further distinguishes SK-HEP-1 cells from many other HCC lines, allowing investigation of DNA damage signaling networks in a context that more closely mirrors certain patient tumors.
INO80C is an essential subunit of the evolutionarily conserved INO80 ATP-dependent chromatin remodeling complex, which facilitates nucleosome sliding and eviction to regulate genome function. It directly interacts with the core ATPase INO80 and accessory subunits including ACTR5 (ARP5), ACTR8, RUVBL1 (TIP49a), RUVBL2 (TIP49b), and the transcription factor YY1. Through these interactions, INO80C modulates chromatin architecture at DNA double-strand breaks, promoting homologous recombination repair by enabling the recruitment of repair factors such as RAD51 and BRCA1. Its activity is activated downstream of the ATM and ATR kinases, which initiate DNA damage responses, and it functions in concert with p53-mediated checkpoints. Additionally, INO80C participates in transcription regulation and replication fork stability, underscoring its multifaceted roles in genome maintenance.
Ablation of INO80C in SK-HEP-1 cells disrupts assembly of a functional INO80 complex, impairing homologous recombination and rendering the cells hypersensitive to DNA-damaging chemotherapeutics like cisplatin and PARP inhibitors. This defect leads to accumulation of unresolved DNA breaks, elevated ??H2AX foci, and increased genomic instability. In the context of hepatocellular carcinoma, INO80C loss may reveal synthetic lethal interactions or vulnerabilities that can be exploited therapeutically. The model also permits dissection of the crosstalk between chromatin remodeling, p53-dependent DNA repair pathways, and transcriptional reprogramming associated with liver cancer progression. Consequently, these knockout cells serve as a powerful tool for uncovering molecular mechanisms that drive hepatic tumorigenesis and drug resistance.
The INO80C Knockout SK-HEP-1 Polyclonal Cells are ideally suited for a broad range of applications. They enable detailed mechanistic studies of INO80C-dependent chromatin remodeling and DNA repair, using readouts such as Western blotting for protein expression, immunofluorescence microscopy for DNA damage foci (??H2AX), and homologous recombination reporter assays. Functional assays can assess sensitivity to DNA-damaging agents (e.g., cisplatin, olaparib) via cell viability measurements, while RNA sequencing can capture transcriptomic alterations. Additional phenotypic analyses may include comet assays for DNA damage quantitation, invasion/migration assays to evaluate metastatic potential, and flow cytometry for cell cycle distribution. For additional technical information or to request a quotation, please contact Ascent Research.
