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- W4386486827 abstract "Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA decay pathway with roles in cellular stress responses, differentiation, and viral defense. It functions in both quality control and post-transcriptional regulation of gene expression. NMD has also emerged as a modulator of cancer progression, although available evidence supports both a tumor suppressor and a pro-tumorigenic role, depending on the model. To further investigate the role of NMD in cancer, we knocked out the NMD factor SMG7 in the HT1080 human fibrosarcoma cell line, resulting in suppression of NMD function. We then compared the oncogenic properties of the parental cell line, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. We also tested the effect of a drug inhibiting the NMD factor SMG1 to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays and a mouse xenograft tumor model, we showed that suppression of NMD function severely compromises the oncogenic phenotype. Molecular pathway analysis revealed that NMD suppression strongly reduces matrix metalloprotease 9 (MMP9) expression and that MMP9 re-expression partially rescues the oncogenic phenotype. Since MMP9 promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation may contribute to the reduced tumorigenicity of NMD-suppressed cells. Collectively, our results highlight the potential value of NMD inhibition as a therapeutic approach." @default.
- W4386486827 created "2023-09-07" @default.
- W4386486827 creator A5043200316 @default.
- W4386486827 creator A5048106842 @default.
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- W4386486827 creator A5059287185 @default.
- W4386486827 creator A5079003233 @default.
- W4386486827 creator A5091298095 @default.
- W4386486827 date "2023-06-09" @default.
- W4386486827 modified "2023-10-16" @default.
- W4386486827 title "Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells" @default.
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