title: MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling.
abstract: 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.
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Jia-Quan
authors: JQ
authors: Qu
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Hong-Mei
authors: HM
authors: Yi
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Xu
authors: X
authors: Ye
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Jin-Feng
authors: JF
authors: Zhu
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Hong
authors: H
authors: Yi
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Li-Na
authors: LN
authors: Li
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Ta
authors: T
authors: Xiao
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Li
authors: L
authors: Yuan
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Jiao-Yang
authors: JY
authors: Li
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Yuan-Yuan
authors: YY
authors: Wang
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Juan
authors: J
authors: Feng
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Qiu-Yan
authors: QY
authors: He
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Shan-Shan
authors: SS
authors: Lu
authors: Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China. The Higher Educational Key Laboratory for Cancer Proteomics and Translational Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, China. zqxiao2001@hotmail.com.
authors: Zhi-Qiang
authors: ZQ
authors: Xiao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy; D010766:Phosphorylation / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D011878:Radiotherapy / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000528:radiation effects; D016019:Survival Analysis; D047368:Tumor Burden / Q000235:genetics / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D016209:Interleukin-8; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt