The DIS3L2 Knockout MES-OV Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the MES-OV human ovarian endometrioid carcinoma cell line, engineered to disrupt the DIS3L2 gene. This product provides a heterogeneous loss-of-function model for investigating the molecular functions of DIS3L2, a 3??-5?? exoribonuclease critical in RNA surveillance and uridylated RNA decay pathways. The polyclonal format reflects a mixed population of cells with diverse CRISPR-mediated gene disruptions, enabling robust functional studies without the clonal variability associated with single-cell-derived lines. Researchers can utilize these cells to interrogate DIS3L2-dependent mechanisms in cancer biology, RNA metabolism, and miRNA regulation, leveraging the intact genetic background of the MES-OV ovarian cancer model.
The host MES-OV cell line is an epithelial, adherent model established from ovarian endometrioid carcinoma, a clinically distinct subtype of epithelial ovarian cancer. It retains key characteristics of ovarian tumor cells, including aberrant signaling networks and metastatic potential, making it a relevant in vitro platform for studying ovarian cancer biology. MES-OV cells are widely used to investigate tumor progression, drug resistance, and the molecular pathways driving endometrioid ovarian carcinomas, providing a physiologically appropriate context for DIS3L2 functional analysis.
DIS3L2 functions as a 3??-5?? exoribonuclease that catalyzes the decay of uridylated RNAs, positioning it as a central post-transcriptional regulator. Within the LIN28/let-7 axis, DIS3L2 is functionally integrated with LIN28 and the terminal uridylyltransferase ZCCHC11: LIN28 recruits ZCCHC11 to uridylate pre-let-7 miRNA precursors, marking them for DIS3L2-mediated degradation by suppressing let-7 biogenesis. This repression of let-7 relieves inhibition on downstream oncogenic targets such as HMGA2 and KRAS. Additionally, DIS3L2 is implicated in the degradation of broader uridylated mRNA substrates and cell cycle-related transcripts, and its activity may be transcriptionally influenced by p53, linking RNA metabolism to tumor-suppressive and cell cycle checkpoint pathways.
In the ovarian cancer context, DIS3L2 deficiency is associated with dysregulated miRNA maturation and altered RNA stability, contributing to oncogenic phenotypes. The MES-OV knockout model enables dissection of DIS3L2??s role in maintaining RNA homeostasis and its impact on ovarian cancer cell proliferation, migration, and survival. Given that DIS3L2 aberrations are observed in Perlman syndrome, colorectal cancer, and multiple myeloma, this system also offers translational insights into tissue-specific RNA decay mechanisms. By eliminating DIS3L2 function, researchers can assess compensatory RNA degradation pathways and the accumulation of uridylated species in an endometrioid carcinoma background.
Typical research applications include mechanistic studies of RNA decay, miRNA biogenesis regulation, and ovarian cancer progression. For example, RT-qPCR and western blotting validate knockout efficiency, while RNA-seq and miRNA qPCR arrays profile transcriptomic and miRNA changes, particularly let-7 family members. Functional assays such as migration, proliferation, and apoptosis assays dissect phenotypic consequences of DIS3L2 loss. This product is also suited for drug resistance experiments and substrate identification via RNA immunoprecipitation or crosslinking approaches. For further information and technical support, please contact Ascent Research.
