The IFI27 Knockout NCI-H1299 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal cell population derived from the human non-small cell lung cancer (NSCLC) line NCI-H1299, carrying a targeted disruption of the IFI27 gene. This polyclonal knockout model provides a genetically heterogeneous pool of cells with loss-of-function of IFI27, enabling robust and reproducible functional studies without the clonal selection bias inherent in monoclonal lines. The product is ideally suited for investigating the role of IFI27 in apoptosis regulation, interferon signaling, and tumor cell survival mechanisms.
NCI-H1299 is a widely used lung adenocarcinoma epithelial cell line established from a lymph node metastasis, characterized by p53 deficiency and a highly metastatic, tumorigenic phenotype. The absence of functional p53 makes these cells a valuable model for studying p53-independent cell death pathways and the molecular drivers of NSCLC progression. The cell line??s origin from a metastatic site further enhances its utility for research on cancer invasion and metastasis, providing a clinically relevant context in which to interrogate the tumor-suppressive functions of interferon-stimulated genes.
IFI27 encodes an interferon-inducible mitochondrial protein that functions as a pro-apoptotic effector in the type I interferon response. Upon stimulation by interferon-alpha or interferon-beta, the JAK1/TYK2 kinases activate STAT1 and STAT2, which together with IRF9 form the ISGF3 complex that transcriptionally induces IFI27. The protein localizes to the mitochondrial inner membrane and interacts with BCL2 family members to promote mitochondrial outer membrane permeabilization (MOMP), facilitating cytochrome c release and subsequent activation of caspase-9 and caspase-3. IFI27 thus acts downstream of the IFNAR1/2 receptor and upstream of the BAX/BAK-mediated apoptotic execution step, directly linking innate immune signaling to mitochondrial apoptosis.
Knockout of IFI27 in the NCI-H1299 p53-null background disrupts interferon-induced apoptosis, creating a model in which tumor cells evade immune-mediated cell death. This genetic context is particularly relevant for studying how NSCLC cells subvert innate immune responses to survive and metastasize. By preventing MOMP and cytochrome c release, IFI27 loss uncouples interferon signaling from the intrinsic apoptotic machinery, allowing systematic dissection of alternative death pathways and survival signaling. Consequently, these polyclonal knockout cells are an essential tool for elucidating the molecular mechanisms underlying resistance to interferon-based therapies and immune evasion in lung cancer.
Potential applications encompass a broad range of functional assays. Researchers can evaluate apoptosis signaling by treating cells with interferon-alpha or -beta and measuring caspase activation via Western blotting or flow cytometry with annexin V staining. Comparative RNA-seq or RT-qPCR profiling of interferon-stimulated gene expression between knockout and wild-type cells reveals IFI27-dependent transcriptional programs. Moreover, the model supports drug sensitivity screening to identify compounds that restore apoptosis in IFI27-deficient cancers, and antiviral pathway analysis by challenging cells with virus-mimicking stimuli. For additional technical details or order inquiries, please contact Ascent Research.
