miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma.

摘要: // Luqing Zhao 1,2,3,4 , Min Tang Zheyu Hu Bin Yan Weiwei Pi 5,6 Zhi Li 5 Jing Zhang 6 Liqin 8 Wuzhong Jiang Guo 7 Yuanzheng Qiu Fang 9 Feng Liu Jingchen Lu 1,6 Xue Chen Lanbo Xiao Zhijie Xu Yongguang Tao Lifang Yang Ann M. Bode 10 Zigang Dong Jian Zhou 11 Jia Fan Lunquan Sun 4,5 and Ya Cao 1 Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China 2 Key Laboratory Carcinogenesis Invasion, Ministry Education, 3 Carcinogenesis, Health, 4 Molecular Imaging Center, Hospital, Center for Department Oncology, Otolaryngology Head Neck Surgery, Radiology, Metabolism Endocrinology The Second Hormel University Minnesota, Austin, MN, USA Live Liver Zhongshan Fudan Shanghai, Correspondence to: Cao, email: Sun, Keywords : miR-504; radio-resistance; nuclear respiratory factor (NRF1); biomarker; nasopharyngeal carcinoma (NPC) Received December 30, 2014 Accepted April 20, 2015 Published May 14, Abstract microRNAs (miRNAs) are involved in the various processes DNA damage repair play crucial roles regulating response tumors to radiation therapy. Here, we used radio-resistant cell lines as models found that expression miR-504 was significantly up-regulated. In contrast, (NRF1) other mitochondrial metabolism factors, including transcription A (TFAM) oxidative phosphorylation (OXPHOS) complex III were down-regulated these lines. At same time, Seahorse stress test results indicated capacity impaired NPC a over-expressing line. We also conducted dual luciferase reporter assays verified could directly target NRF1. Additionally, down-regulate TFAM OXPHOS complexes I, III, IV function cells. Furthermore, serum from patients showed up-regulated during different weeks radiotherapy correlated with tumor, lymph nodes metastasis (TNM) stages total tumor volume. radio-therapeutic effect at three months after evaluated. Results high exhibited relatively lower therapeutic ratio complete (CR), but higher partial (PR), compared low miR-504. Taken together, demonstrated affected radio-resistance by down-regulating NRF1 disturbing function. Thus, might become promising biomarker targeting improve response.