MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling
| Autor: | Qiu-Yan He, Yuan-Yuan Wang, Jiao-Yang Li, Hong-Mei Yi, Li Yuan, Juan Feng, Xu Ye, Zhi-Qiang Xiao, Li-Na Li, Ta Xiao, Jing-Feng Zhu, Hong Yi, Jia-Quan Qu, Shan-Shan Lu |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Cell Blotting Western Mice Nude Apoptosis Biology Radiation Tolerance Radioresistance Cell Line Tumor microRNA otorhinolaryngologic diseases medicine Animals Humans Interleukin 8 Phosphorylation Protein kinase B 3' Untranslated Regions Nasopharyngeal Carcinoma Radiotherapy Microarray analysis techniques Reverse Transcriptase Polymerase Chain Reaction Carcinoma Interleukin-8 Cancer Nasopharyngeal Neoplasms medicine.disease Molecular biology Immunohistochemistry Survival Analysis Xenograft Model Antitumor Assays Tumor Burden Gene Expression Regulation Neoplastic stomatognathic diseases MicroRNAs medicine.anatomical_structure Oncology Nasopharyngeal carcinoma Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Molecular cancer therapeutics. 14(11) |
| ISSN: | 1538-8514 |
| Popis: | Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA (miR) regulates this phenomenon. In this study, we investigated the function and mechanism of miR-203 in NPC radioresistance, one of downregulated miRs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-203 was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its decrement significantly correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that miR-203 mimic markedly decreased NPC cell radioresistance. In a mouse model, therapeutic administration of miR-203 agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we confirmed that IL8 was a direct target of miR-203, and found that reduced miR-203 promoted NPC cell radioresistance by activating IL8/AKT signaling. Moreover, the levels of IL8 and phospho-AKT were significantly increased in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and negatively associated with miR-203 level. Our data demonstrate that miR-203 is a critical determinant of NPC radioresponse, and its decrement enhances NPC radioresistance through targeting IL8/AKT signaling, highlighting the therapeutic potential of the miR-203/IL8/AKT signaling axis in NPC radiosensitization. Mol Cancer Ther; 14(11); 2653–64. ©2015 AACR. |
| Databáze: | OpenAIRE |
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