The DIS3L2 Knockout NCI-H1299 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population designed for loss-of-function analysis of the DIS3L2 gene. This product is derived from the NCI-H1299 cell line and features heterogeneous gene disruption across the cell pool, avoiding clonal selection bias while enabling functional studies in a physiologically relevant NSCLC context. The knockout model provides a powerful tool for dissecting DIS3L2-dependent mechanisms in lung cancer biology.
The parental NCI-H1299 cell line is a widely utilized model of non-small cell lung carcinoma, originally established from a metastatic lymph node of a patient with lung adenocarcinoma. These cells harbor a homozygous deletion of the TP53 gene, rendering them p53-null, which is a common feature in aggressive lung cancers. The NCI-H1299 line is extensively employed in NSCLC research for studying tumor cell proliferation, apoptosis, drug resistance, and signaling pathways due to its defined genetic background and reproducible growth characteristics.
DIS3L2 encodes a 3′-5′ exoribonuclease that degrades uridylated RNAs, functioning in RNA surveillance and tumor suppression. It acts downstream of LIN28A and the uridyltransferases TUT4/TUT7, which add uridine tails to precursor miRNAs like pre-let-7. DIS3L2 then degrades these uridylated transcripts to enable mature let-7 biogenesis. Knockout of DIS3L2 causes accumulation of uridylated pre-let-7, reducing mature let-7 levels and thereby relieving miRNA-mediated repression of downstream targets such as cell cycle regulators and p53 pathway effectors. DIS3L2 also interacts with LIN28B, further integrating this exonuclease into miRNA biogenesis and global RNA metabolism.
In the p53-null NCI-H1299 background, DIS3L2 knockout provides a unique tool to study tumor suppressor mechanisms independent of p53. Let-7 miRNAs target oncogenes including RAS and HMGA2; thus, loss of DIS3L2 may heighten tumorigenic potential through sustained oncogene expression. This model is particularly suited for examining LIN28/let-7 axis functions in lung cancer and identifying p53-independent growth controls or synthetic vulnerabilities. Additionally, the metastatic origin of NCI-H1299 cells allows investigation of DIS3L2??s role in NSCLC progression and metastasis.
Typical applications include western blotting, RT-qPCR for let-7 quantification, RNA-seq, proliferation assays, apoptosis assays, and drug sensitivity screening. Researchers can use these polyclonal knockout cells for functional dissection of DIS3L2 in lung cancer, LIN28/let-7 pathway analysis, tumor suppressor studies, and drug response profiling. Rescue experiments and high-throughput screens are also feasible. For additional information or support, contact Ascent Research.
