The DIS3L2 Knockout 786-O Polyclonal Cells consist of a heterogeneous 786-O cell population engineered by CRISPR/Cas9-mediated gene disruption to eliminate functional DIS3L2 expression. As a polyclonal knockout pool, this product avoids clonal selection biases and preserves edited-population diversity, offering a robust loss-of-function model for studying DIS3L2-dependent RNA decay and tumor suppression.
The host 786-O cell line, derived from a primary clear cell renal cell carcinoma (ccRCC) of a 58-year-old male, carries a VHL frameshift mutation at codon 104, making it deficient in VHL tumor suppressor activity. This VHL-deficient background recapitulates a hallmark of ccRCC and provides a clinically relevant renal cancer context for investigating DIS3L2 functions.
DIS3L2 is a 3??-5?? exoribonuclease that degrades uridylated RNAs, notably pre-let-7 miRNA precursors, upon uridylation by TUT4/ZCCHC11 or TUT7/ZCCHC6. The RNA-binding proteins LIN28A/B recruit these TUTases to pre-let-7, promoting DIS3L2-dependent decay. Knockout of DIS3L2 leads to pre-let-7 accumulation, reduced mature let-7 levels, and derepression of oncogenic targets HMGA2 and RAS. DIS3L2 also participates in general mRNA surveillance and interacts with P-body components, thereby influencing cell cycle regulation and Wnt signaling.
In 786-O cells, loss of DIS3L2 disrupts miRNA-mediated tumor suppression in a VHL-deficient setting, driving oncogenic gene expression and enhanced tumorigenic properties. This model is instrumental for dissecting cooperative interactions between DIS3L2 and other renal cancer pathways, and for exploring Perlman syndrome and Wilms tumor mechanisms linked to DIS3L2 mutations.
Typical research applications include RT-qPCR for pre-let-7 and mature let-7 quantification, western blotting for DIS3L2 confirmation, RNA-seq transcriptome analysis, and miRNA profiling. Functional assays such as cell proliferation, migration, invasion, and xenograft tumor models can assess tumorigenic phenotypes, while the polyclonal format facilitates high-throughput drug screening. For more details, please contact Ascent Research.
