ACOD1 Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the UM-UC-3 human bladder carcinoma epithelial cell line, with targeted disruption of the ACOD1 gene (also known as IRG1). This loss-of-function model enables study of itaconate metabolism in a tumorigenic bladder cancer context without relying on single-cell clonal expansion. The polyclonal pool retains heterogeneous editing events across the target locus, providing a population-level knockout suitable for functional assays.
UM-UC-3 is a human male-derived transitional cell carcinoma line with wild-type TP53, widely used as a model of bladder cancer tumorigenesis and epithelial malignancy. These cells exhibit classic carcinoma hallmarks and are instrumental for dissecting oncogenic signaling, metabolic adaptation, and immune interactions characteristic of bladder tumors. The established background of UM-UC-3 offers a reproducible platform for investigating how ACOD1 disruption influences cancer cell biology.
ACOD1 encodes aconitate decarboxylase 1, which converts cis-aconitate to itaconate, a metabolite with potent anti-inflammatory properties. ACOD1 expression is robustly induced by inflammatory stimuli such as LPS/TLR4 signaling, TNF-??, and IFN-??, acting through transcription factors NF-??B, IRF1, and STAT1. Itaconate exerts its effects by alkylating KEAP1, leading to Nrf2 stabilization and antioxidant response activation, and by inhibiting succinate dehydrogenase (SDH), thereby modulating the TCA cycle. Additionally, itaconate directly targets glycolytic enzymes GAPDH and LDHA, and suppresses NLRP3 inflammasome activation, resulting in reduced IL-1?? production and upregulation of ATF3. This positions ACOD1 at a critical node linking metabolic and inflammatory pathways.
In bladder cancer, inflammatory signaling and metabolic reprogramming are key drivers of tumor progression and immune evasion. The ACOD1 Knockout UM-UC-3 Polyclonal Cells allow researchers to dissect the cell-autonomous role of itaconate production in these processes. By ablating ACOD1, one can assess changes in Nrf2-mediated antioxidant defenses, SDH-dependent succinate accumulation, glycolytic flux, and NLRP3 inflammasome activity within a bladder carcinoma background. This model is particularly valuable for evaluating how loss of itaconate synthesis affects tumor cell viability, migration, and interaction with immune components, providing insights into potential therapeutic vulnerabilities.
Researchers can employ this model in a variety of experimental contexts, including metabolic flux analysis by Seahorse to measure oxidative phosphorylation and glycolysis, LC-MS quantification of itaconate levels, Nrf2 reporter assays, and SDH activity measurements. Co-culture experiments with immune cells enable investigation of how ACOD1 deficiency in tumor cells alters cytokine profiles and NLRP3 inflammasome activation in the microenvironment. Further applications include assessing migration and invasion potential, evaluating responses to standard chemotherapies or immunotherapies, and probing roles in inflammatory bowel disease or sepsis models. For additional information or technical support, please contact Ascent Research.
