The HNRNPDL Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population generated from the NCI-H1975 human lung adenocarcinoma cell line. This product features a polyclonal pool of cells harboring CRISPR/Cas9-mediated gene disruption at the endogenous HNRNPDL locus, providing a heterogeneous loss-of-function model for studying the biological roles of the HNRNPDL RNA-binding protein.
The parental NCI-H1975 cell line was originally established from the pleural effusion of a non-smoking female with lung adenocarcinoma and serves as a well-characterized in vitro model of non-small cell lung carcinoma (NSCLC). These epithelial cells retain key genetic and phenotypic features of the original tumor, including activating mutations in EGFR, making them particularly relevant for investigating lung cancer biology and therapeutic responses.
HNRNPDL is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family and functions as a regulator of alternative splicing and mRNA stability. It interacts directly with other splicing factors such as HNRNPA1, HNRNPA2B1, and SRSF1, and associates with the spliceosome and RNA polymerase II to modulate splicing decisions. Its activity is modulated by upstream kinases including SR protein kinases (SRPKs) and CDC-like kinases (CLKs), and its expression is positively regulated by the MYC transcription factor. Downstream of HNRNPDL, alternative splicing of key targets is affected; these include TP53 isoforms, CD44 splice variants, and CTNND1, which encode proteins involved in tumor suppression, cell adhesion, and epithelial-mesenchymal transition (EMT). Consequently, HNRNPDL sits at the nexus of pathways controlling splicing-dependent regulation of EMT and tumorigenic gene expression programs.
In the context of NCI-H1975 NSCLC cells, disruption of HNRNPDL expression is expected to impair the normal splicing patterns of its target pre-mRNAs, leading to altered isoform ratios of functionally important proteins such as p53 and CD44. This perturbation can affect cellular processes including proliferation, migration, invasion, and apoptosis, thereby providing a physiologically relevant platform to dissect the role of hnRNP-mediated splicing in lung cancer pathogenesis and EMT regulation. The polyclonal nature of the knockout pool allows researchers to observe averaged phenotypic effects while avoiding clonal selection biases.
This polyclonal knockout model is suited for a wide array of functional genomics and mechanistic studies. Researchers can employ RT-PCR and RNA-seq to analyze transcriptome-wide splicing changes, and western blotting with isoform-specific antibodies to quantify protein-level alterations. RNA immunoprecipitation (RIP) can be used to assess RNA-protein interactions in the absence of HNRNPDL. Functional assays such as MTS/XTT proliferation assays, Transwell migration/invasion assays, and Annexin V apoptosis assays are directly applicable to evaluate phenotypic consequences. The cells are also valuable for drug target validation in splicing-modulating therapies and for high-throughput screening campaigns. For further information, please contact Ascent Research.
