The DIS3L2 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line. This product features targeted disruption of the DIS3L2 gene, generating a heterogeneous pool of cells with loss-of-function alleles that enables robust assessment of DIS3L2-dependent phenotypes without clonal selection artifacts. The polyclonal format provides a practical loss-of-function model for pooled functional studies, reducing the risk of clonal variability and off-target complications inherent to single-cell-derived lines.
The AGS parental cell line was originally established from a human gastric adenocarcinoma and is characterized as an adherent epithelial cell model. AGS cells are widely employed in cancer research due to their tumorigenic properties, well-defined molecular profile, and suitability for investigating gastric cancer pathogenesis, drug sensitivity, and signal transduction. This knockout model thus retains the gastric cancer-relevant genetic background while disrupting a key RNA surveillance pathway, offering a powerful tool for dissecting RNA metabolism in gastric tumor biology.
DIS3L2 encodes a 3??-5?? exoribonuclease that functions as a central effector of uridylation-mediated RNA decay. The enzyme is recruited to substrate RNAs tagged with non-templated oligo-U tails added by the terminal uridylyltransferases TUT4 and TUT7, and it processively degrades these transcripts. Its targets include let-7 miRNA precursors and mRNAs bearing short poly(A) tails, thereby regulating miRNA biogenesis and global mRNA turnover. DIS3L2 cooperates with the exosome complex, specifically interacting with core subunits such as EXOSC10, to coordinate cytoplasmic RNA degradation. Through these interactions, DIS3L2 modulates the abundance of tumor-suppressive let-7 miRNAs and downstream protein coding transcripts, establishing a critical node in post-transcriptional gene regulation.
In the AGS gastric cancer context, disruption of DIS3L2 is expected to impair the uridylation-dependent decay pathway, leading to accumulation of pre-let-7 miRNAs and consequent dysregulation of their mature forms. This disruption can result in altered expression of oncogenic targets normally repressed by let-7, including regulators of cell proliferation and survival. While DIS3L2 mutations are associated with developmental syndromes like Perlman syndrome and Wilms tumor, its role in gastric adenocarcinoma remains an active area of investigation. The AGS knockout model thus provides a relevant human cell background to study how perturbed RNA surveillance contributes to gastric cancer cell phenotypes, including proliferation, migration, and drug response.
This polyclonal knockout cell product is ideally suited for a range of experimental applications in RNA biology and oncology. Researchers can use it for mechanistic studies of miRNA biogenesis, RNA decay kinetics, and target mRNA identification via RNA-seq. Functional assays such as cell viability, proliferation, and migration/invasion can be employed to evaluate the impact of DIS3L2 loss on gastric cancer cell behavior. The model is also well adapted for drug sensitivity screening, allowing assessment of chemotherapeutic responses in the context of compromised RNA surveillance. For additional technical information or ordering inquiries, please contact Ascent Research.
