The HNRNPAB Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population engineered for targeted disruption of the HNRNPAB gene in the NCI-H1975 lung adenocarcinoma background. This product offers a genetically heterogeneous knockout model generated by transient transfection of Cas9 and guide RNAs, resulting in a mixed population of edited allele states. The polyclonal format is well-suited for pooled functional screens and studies requiring averaging of clonal variation, providing a robust loss-of-function model without the need for single-cell cloning. It enables investigation of HNRNPAB-dependent phenotypes in a therapeutically relevant non-small cell lung cancer context.
NCI-H1975 is a human lung adenocarcinoma cell line harboring activating EGFR L858R and T790M mutations, commonly used to study EGFR-mutant non-small cell lung cancer and drug resistance. These cells are derived from a female non-smoker and exhibit dependency on EGFR signaling, with the T790M mutation conferring resistance to first-generation tyrosine kinase inhibitors. They serve as a standard model for evaluating third-generation EGFR inhibitors and investigating bypass resistance mechanisms.
HNRNPAB encodes an RNA-binding protein of the hnRNP family that regulates pre-mRNA splicing, nucleocytoplasmic transport, and telomere maintenance. It interacts with spliceosomal components, HNRNPA1, and HNRNPA2B1 to modulate alternative splicing of proliferation- and survival-associated transcripts. In the telomere axis, HNRNPAB binds TERC and associates with TERT, facilitating telomerase assembly and activity. Upstream regulatory mechanisms are not well-defined, but post-translational modifications may alter its RNA-binding properties. Through these dual roles, HNRNPAB integrates RNA processing with telomere biology to sustain genomic stability and cell proliferation.
Knockout of HNRNPAB in the EGFR-mutant NCI-H1975 line offers insight into the interplay between RNA metabolism and telomere regulation in lung adenocarcinoma. Loss of HNRNPAB may compromise telomere maintenance, triggering telomere shortening and growth arrest, while aberrant splicing could dysregulate pathways that synergize with oncogenic EGFR signaling, potentially influencing drug sensitivity. This model enables dissection of HNRNPAB??s contribution to the transcriptomic changes seen in drug-tolerant states and may uncover novel vulnerabilities for therapeutic targeting.
Typical experiments include transcriptome-wide splicing analysis by RNA-seq, RNA immunoprecipitation (RIP) of HNRNPAB and interacting proteins, RT-qPCR quantification of target transcripts, telomerase activity measurement via TRAP assay, and cell proliferation and apoptosis assays. Drug sensitivity profiling can be performed with EGFR inhibitors (e.g., osimertinib) to assess whether HNRNPAB loss re-sensitizes resistant cells. The polyclonal population is advantageous for pooled functional genomics and compound screens seeking to modulate RNA processing or telomere biology. Researchers studying HNRNPAB in NSCLC pathobiology, drug resistance, and RNA-protein interactions will find this product a valuable resource. For additional information, please contact Ascent Research.
