Purpose: Ionizing radiation (IR) is widely used for treating nasopharyngeal carcinoma (NPC). However, recent studies indicate that IR can also promote the migration and invasion of malignant tumors. Phosphatase 1 nuclear-targeting subunit (PNUTS), a novel interacting protein, was recently demonstrated to be involved in tumorigenesis and metastasis formation. This protein was hypothesized to take part in IR-induced migration and invasion in NPC cells in this study.
Materials and methods: Western blotting was used to detect how PNUTS was expressed in NPC cells with or without IR treatment. Wound-healing and Transwell assays were used to measure cell migration and invasion. Quantitative real-time PCR and Western blotting were used to determine the expression levels of PNUTS and epithelial–mesenchymal transition (EMT) proteins, respectively, after CNE-2 cells were infected with an adenovirus vector, ad-PNUTS, or transfected with PNUTS-specific siRNA. Finally, the expression levels of PI3K/AKT signaling-related proteins were detected by Western blotting.
Results: IR significantly promoted PNUTS expression and the migration and invasion in CNE-2 cells. Moreover, after exposure to IR, expression of the mesenchymal markers N-cadherin and vimentin increased, while that of the epithelial marker E-cadherin decreased. Silencing PNUTS remarkably attenuated IR-induced increases in cell migration and invasion and reversed the EMT process. Additionally, the overexpression of PNUTS restored the mobility and invasiveness of CNE-2 cells, which regained EMT characteristics. Furthermore, we found that PNUTS regulated IR-induced EMT via the PI3K/AKT signaling pathway.
Conclusion: Our research illustrates a relationship between PNUTS and IR-induced cell migration and invasion and provides a novel therapeutic target for preventing radiotherapy-induced metastasis in NPC patients.
Keywords: PNUTS, ionizing radiation, EMT, PI3K/AKT pathway, NPC