HEATR3 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited human cell population harboring a targeted disruption of the HEATR3 gene. This polyclonal knockout pool is derived from NCI-H1975 cells engineered to introduce loss-of-function mutations in HEATR3, generating a heterogeneous collection of edited alleles. The knockout model facilitates investigation of HEATR3 function without requiring clonal isolation, providing a versatile tool for studying phenotypes that may be influenced by polyclonal variation. This product is supplied as a live cell population suitable for immediate expansion and use in downstream functional assays.
The host cell line, NCI-H1975, is a widely used non-small cell lung cancer model originally derived from a lung adenocarcinoma patient. These cells exhibit epithelial morphology and harbor the activating EGFR L858R mutation, which drives oncogenic signaling through pathways such as RAS-MAPK and PI3K-AKT-mTOR. NCI-H1975 cells are commonly employed to study EGFR-targeted therapy resistance and the role of ribosomal alterations in cancer biology. The epithelial NCI-H1975 background provides a physiologically relevant context for examining how HEATR3 disruption impacts cancer cell growth and survival.
HEATR3 encodes a HEAT-repeat-containing protein that functions as a critical scaffold in pre-ribosomal RNA processing and 90S pre-ribosome assembly. It interacts with multiple small subunit processome components, including UTP18, UTP6, WDR43, PWP2, and NOL6, facilitating the maturation of 18S rRNA and formation of the small ribosomal subunit. HEATR3 transcription is positively regulated by MYC and mTORC1, while p53 can suppress its expression under stress conditions. Downstream, HEATR3 activity promotes 18S rRNA maturation and global protein synthesis, linking growth signaling to ribosome biogenesis.
In the NCI-H1975 context, HEATR3 knockout is expected to impair ribosome production, potentially slowing cell proliferation and altering sensitivity to therapies that target ribosome biogenesis or protein synthesis. Because NCI-H1975 cells rely on hyperactive MYC and mTORC1 networks, HEATR3 disruption may uncouple growth factor signaling from translational output, providing a model to study synthetic lethal interactions or ribosomopathy phenotypes. This knockout population can be used to explore mechanisms underlying Diamond-Blackfan anemia and other ribosomopathies in a cancer cell backdrop.
Researchers can utilize HEATR3 Knockout NCI-H1975 Polyclonal Cells for a range of functional assays, including colony formation, proliferation, polysome profiling, puromycin incorporation, and drug sensitivity testing against mTOR inhibitors or RNA polymerase I inhibitors. Transcriptional profiling by RNA-seq or RT-qPCR can reveal compensatory responses to ribosome biogenesis stress, while western blotting enables monitoring of ribosomal protein levels and signaling pathway activity. These applications support studies in cancer biology, ribosome biogenesis, and functional genomics. For additional information or technical support, please contact Ascent Research.
