OncoTargets and Therapy (Feb 2019)
PNUTS mediates ionizing radiation-induced CNE-2 nasopharyngeal carcinoma cell migration, invasion, and epithelial–mesenchymal transition via the PI3K/AKT signaling pathway
Abstract
Dan Yu, Xiang An, Wanlin Fan, Xin Wang, Yuxing He, Bing Li Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China 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
