Yuanjian Huang1, Duxun Tan2, Juan Xiao1, Qiaoyun Li1, Xianfeng Zhang1, Zhiqiang Luo1. 1. Department of Otorhinolaryngology, The Second Affiliated Hospital, University of South China, Hengyang, China. 2. Department of Emergency, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.
Abstract
INTRODUCTION: Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. MATERIALS AND METHODS: A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells. RESULTS: In this study, a cell line CNE-2R derived from parental CNE-2 was established via being exposed to stepwise escalated radiation dose. The expression of miR-150 was upregulated in CNE-2R cells. The radioresistance of CNE-2R cells was reversed after inhibiting miR-150 with specific inhibitor, while the radioresistance of CNE-2 cells was enhanced after the overexpression of miR-150. MiR-150b elicited these responses by directly targeting GSK3β. Moreover, GSK3β protein expression was downregulated in CNE-2R cells and restored GSK3β expression increased radiosensitivity of CNE-2R cells. Importantly, the negative correlation between miR-150 expression and GSK3β protein level was confirmed in the NPC tissues. High miR-150 expression and low GSK3β protein level were associated with poor prognosis in NPC patients. CONCLUSION: Our findings suggested that miR-150-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for NPC treatment.
INTRODUCTION: Radiotherapy has been the primary treatment for nasopharyngeal carcinoma (NPC), but the NPC radiocurability was severely limited with the radioresistance. The research suggested the important role of miRNAs in cancer therapeutic response. MATERIALS AND METHODS: A radioresistant NPC cell line CNE-2R, we exposed CNE-2 cells to a range of radiation doses. Levels of miR-150 were measured by quantitative reverse-transcriptase polymerase chain reaction in CNE-2R and CNE-2 cells. RESULTS: In this study, a cell line CNE-2R derived from parental CNE-2 was established via being exposed to stepwise escalated radiation dose. The expression of miR-150 was upregulated in CNE-2R cells. The radioresistance of CNE-2R cells was reversed after inhibiting miR-150 with specific inhibitor, while the radioresistance of CNE-2 cells was enhanced after the overexpression of miR-150. MiR-150b elicited these responses by directly targeting GSK3β. Moreover, GSK3β protein expression was downregulated in CNE-2R cells and restored GSK3β expression increased radiosensitivity of CNE-2R cells. Importantly, the negative correlation between miR-150 expression and GSK3β protein level was confirmed in the NPC tissues. High miR-150 expression and low GSK3β protein level were associated with poor prognosis in NPC patients. CONCLUSION: Our findings suggested that miR-150-GSK3β axis may be a novel candidate for developing rational therapeutic strategies for NPC treatment.