The HNRNPLL Knockout NCI-H1975 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population designed for functional studies of heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) in a human lung adenocarcinoma background. This product provides a pool of NCI-H1975 cells carrying diverse disruptions in the HNRNPLL gene, generated via CRISPR/Cas9-mediated gene disruption, enabling loss-of-function analysis while capturing cellular heterogeneity. It serves as a versatile tool for investigating the role of HNRNPLL in alternative splicing regulation within a cancer cell context, without requiring single-cell cloning.
NCI-H1975 is a human non-small cell lung cancer (NSCLC) cell line derived from the pleural effusion of a lung adenocarcinoma patient. This line harbors activating mutations in EGFR (L858R and T790M) and PIK3CA, making it a widely used model for studying oncogenic signaling, drug resistance mechanisms, and immune evasion in lung adenocarcinoma. Its epithelial origin and genetic background provide a clinically relevant platform for exploring tumor-intrinsic splicing programs and their impact on cancer biology.
HNRNPLL encodes an RNA-binding protein that functions as a key regulator of alternative splicing, particularly in T cells, where it directs isoform switching of CD45, CTLA-4, and CD44. Its expression is induced upon T-cell receptor (TCR) stimulation via a signaling cascade involving LCK, ZAP70, PLC??1, calcium flux, and NFAT transcription factor dephosphorylation; NF-??B signaling also contributes to its induction. HNRNPLL interacts with splicing factors such as SRSF1, SRSF2, and hnRNP L, and modulates splice site selection in immune receptor transcripts. This network links extracellular immune signals to post-transcriptional control of surface antigen diversity.
In the context of NCI-H1975 lung adenocarcinoma cells, disruption of HNRNPLL may alter the splicing of endogenously expressed immune-related transcripts, potentially affecting the repertoire of surface antigens involved in immune recognition and evasion. Because this cell line does not normally express CD45, the impact on CD45 isoforms may be limited, but other targets such as CD44 and CTLA-4?Crelated splice variants could be perturbed. The polyclonal knockout model thus offers a system to examine how tumor-intrinsic splicing changes influence interactions with the immune microenvironment, without the confounding effects of T-cell signaling machinery typically required for HNRNPLL expression in lymphocytes.
This knockout tool is well-suited for a range of research applications, including mechanistic studies of alternative splicing in cancer, investigation of tumor-immune interactions, and functional genomics screens. Researchers can characterize splicing outcomes using RT-PCR for specific isoforms, explore protein-level changes via western blotting, and assess cell surface antigen profiles by flow cytometry. Transcriptome-wide analysis through RNA-seq can reveal global splicing shifts, while functional assays such as cell proliferation, migration, and invasion experiments allow assessment of phenotypic consequences. For additional details or technical support, please contact Ascent Research.
