The DIS3L2 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal cell population designed to disrupt the DIS3L2 gene in the human NCI-H1975 non-small cell lung cancer cell line. This polyclonal knockout product provides a genetically heterogeneous loss-of-function model, enabling studies of DIS3L2-dependent RNA decay and its roles in tumor biology without clonal isolation. CRISPR-mediated gene disruption generates a population with variable knockout alleles, suitable for functional genomics and pathway analysis.
The parental NCI-H1975 cell line is an epithelial model of human lung adenocarcinoma and harbors well-characterized activating mutations in EGFR and KRAS. Widely used in non-small cell lung cancer research, these cells facilitate investigations into oncogenic signaling, drug resistance, and metastasis.
DIS3L2 is a 3??-5?? exoribonuclease that degrades oligouridylated RNA substrates, notably pre-let-7 miRNAs. In the LIN28/let-7 pathway, LIN28A recruits terminal uridylyltransferases TUT4 (ZCCHC11) and TUT7 (ZCCHC6) to add oligo(U) tails to pre-let-7, creating substrates for DIS3L2-mediated decay. Thus, DIS3L2 acts downstream of LIN28A and TUT4/7 to control mature let-7 biosynthesis. Knockout of DIS3L2 impairs pre-let-7 clearance, leading to reduced mature let-7 levels and consequent upregulation of oncogenic targets such as RAS and HMGA2, linking RNA decay directly to tumor suppression.
In NCI-H1975 cells, which carry activating EGFR and KRAS mutations, loss of DIS3L2 may exacerbate dysregulation of the let-7 tumor suppressor network, potentially enhancing downstream oncogenic signaling and contributing to a more aggressive phenotype. This model is therefore especially suited for studying cooperative interactions between miRNA processing defects and driver oncogene mutations in NSCLC.
This DIS3L2 polyclonal knockout is ideal for investigating mechanisms of RNA uridylation and decay, miRNA regulation, and cancer biology. Typical assays include RT-qPCR and northern blotting for let-7 analysis, western blotting for DIS3L2 verification, RNA-seq for transcriptome profiling, and functional assays such as proliferation, apoptosis, and colony formation. The cells also support drug sensitivity studies and disease modeling of Perlman syndrome and Wilms tumor. For further details, please contact Ascent Research.
