The HDLBP Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited human polyclonal knockout cell population derived from the NCI-H1975 lung adenocarcinoma epithelial cell line. This product provides a heterogeneous pool of cells with targeted disruption of the HDLBP gene, offering a loss-of-function model for studying Vigilin functions in RNA regulation and cholesterol metabolism. The polyclonal format preserves the diversity of gene-editing events, enabling robust phenotypic analysis without clonal selection bias. The cell population is suitable for immediate functional assessments in a tumorigenic lung epithelial background.
The NCI-H1975 host cell line is a widely used non-small cell lung adenocarcinoma model harboring activating EGFR L858R and resistance-associated T790M mutations. These tumorigenic epithelial cells exhibit constitutive EGFR signaling and are extensively employed to investigate mechanisms of targeted therapy sensitivity and resistance. Integrating HDLBP knockout into this genetic context permits the exploration of how post-transcriptional regulation by an RNA-binding protein interfaces with oncogenic EGFR signaling in lung cancer.
HDLBP, also known as Vigilin, encodes a highly conserved RNA-binding protein that associates with HDL particles and polyribosomes. It binds to the 3?? untranslated regions of target mRNAs, including APOA1, LDLR, and ABCA1, thereby modulating their translation and stability. Through interactions with APOA1, APOE, ribosomal subunits, and the translation initiation factor eIF4E, HDLBP scaffolds the coordination of mRNA translation with lipid loading. Upstream, HDLBP expression is transcriptionally regulated by SREBF1 and the liver X receptor NR1H3, and is also responsive to insulin, linking its activity to cellular cholesterol status. Downstream, HDLBP influences the expression of cholesterol transporters ABCA1 and ABCG1, and the receptor LDLR, thereby facilitating cholesterol efflux and uptake. This functional network positions HDLBP at the intersection of HDL receptor signaling and mRNA translation regulation.
In EGFR-mutant lung adenocarcinoma, dysregulation of cholesterol metabolism has been implicated in tumor progression and drug resistance. HDLBP modulates intracellular cholesterol levels and membrane lipid composition, potentially affecting EGFR localization and signaling output. The knockout of HDLBP in NCI-H1975 cells enables the dissection of how proliferative and survival signals driven by mutant EGFR may depend on HDLBP-mediated post-transcriptional control. Furthermore, this model can reveal whether HDLBP contributes to adaptive responses of NSCLC cells to EGFR tyrosine kinase inhibitors, providing insights into resistance mechanisms.
Researchers can utilize these HDLBP knockout polyclonal cells in diverse functional assays, including Western blotting and RT-qPCR to confirm gene disruption and monitor downstream targets, cholesterol efflux assays to assess lipid transport, and RNA immunoprecipitation to study RNA-protein interactions. Cell-based phenotypic analyses such as migration assays and EGFR inhibitor sensitivity testing allow investigation of HDLBP??s role in metastatic potential and therapeutic response. These cells support co-culture experiments, signaling pathway dissection, and comparative studies with wild-type NCI-H1975 cells. For further technical information or to request a quotation, please contact Ascent Research.
