The GPATCH11 Knockout NCI-H1975 Polyclonal Cells consist of a CRISPR/Cas9-edited polyclonal population of the human lung adenocarcinoma cell line NCI-H1975, in which the GPATCH11 gene has been disrupted to create a loss-of-function model. This gene-edited product is designed for researchers investigating the role of GPATCH11 in RNA metabolism and cancer cell biology. The polyclonal nature of the knockout pool ensures a mixture of edited cells, avoiding clonal artifacts and providing a more representative average of gene disruption effects compared to clonal lines. The population is suitable for a variety of downstream assays that require stable knockout of GPATCH11 without the need for single-cell isolation. The cells are provided as a ready-to-use population that can be expanded for multiple experiments, ensuring consistent genetic background and knockout efficiency.
NCI-H1975 is a well-established human non-small cell lung adenocarcinoma cell line derived from a female patient. It harbors an activating EGFR L858R mutation in the tyrosine kinase domain, a key driver of lung oncogenesis, along with a loss-of-function mutation in the tumor suppressor TP53. These genetic alterations are common in lung adenocarcinoma and render the cells dependent on EGFR signaling for survival and proliferation. The cell line is widely used as a model for studying EGFR-mutant lung cancer, including mechanisms of targeted therapy resistance and the biology of TP53-deficient backgrounds. This makes NCI-H1975 an ideal host for investigating the functional relevance of GPATCH11 in a clinically relevant oncogenic context.
GPATCH11 is a G-patch domain-containing protein that functions as an essential cofactor for the DEAH-box RNA helicase DHX15. It stimulates ATP-dependent RNA unwinding during two fundamental processes: pre-mRNA splicing and ribosome biogenesis. Within the spliceosome, GPATCH11 associates with DHX15 and the U5 small nuclear ribonucleoprotein particle (snRNP), facilitating the remodeling events required for intron removal. In ribosome assembly, it interacts with DHX15 and the AAA-ATPase NVL within pre-ribosomal particles, contributing to the maturation of ribosomal RNA. GPATCH11 expression is transcriptionally controlled by the MYC oncogene and is responsive to mTOR signaling, thereby linking cell growth signals to the coordination of splicing and ribosome production. Consequently, loss of GPATCH11 disrupts spliceosome dynamics and ribosomal RNA processing, resulting in widespread alterations in gene expression and impaired cell proliferation.
In the NCI-H1975 lung adenocarcinoma background, the GPATCH11 knockout provides a powerful platform for investigating how dysregulation of RNA metabolism contributes to cancer phenotypes. EGFR-mutant lung cancers frequently exhibit elevated ribosome biogenesis and altered splicing patterns to support uncontrolled proliferation, and GPATCH11 is critically involved in both processes. The presence of a TP53 mutation in these cells further compromises genomic integrity, potentially creating synthetic vulnerabilities that can be uncovered by GPATCH11 depletion. Researchers can use this model to study the interplay between oncogenic EGFR signaling, MYC-driven transcription, and RNA processing factors. Moreover, it allows the examination of GPATCH11 as a candidate target in EGFR-mutant lung adenocarcinoma, particularly in the context of therapeutic resistance.
This polyclonal knockout cell product enables a broad spectrum of functional assays in the fields of RNA biology and cancer research. Western blotting can be used to confirm loss of GPATCH11 protein, while RT-qPCR and RNA sequencing provide quantitative and global views of transcriptomic changes, including splicing alterations and ribosomal RNA processing defects. Cell proliferation and apoptosis assays permit the evaluation of growth phenotypes, and splicing reporter constructs enable the direct measurement of splicing efficiency changes. These cells are valuable for mechanistic studies of GPATCH11??s role in DHX15-mediated RNA unwinding, for high-throughput screening of compounds that synergize with GPATCH11 loss, and for investigating the role of RNA metabolism in drug resistance mechanisms. Researchers can also exploit the model to identify synthetic lethal interactions with EGFR or TP53 mutations, aiding in the development of novel therapeutic strategies. For additional product information, please contact Ascent Research.
