Cao Ke, Li Jingjing, Chen Jia, Qian Li, Wang Aijun, Chen Xiang, Xiong Wei, Tang Jintian, Tang Shijie, Chen Yong, Chen Yao, Cheng Yan, Zhou Jianda
Department of Oncology of Third Xiangya Hospital, Central South University, Changsha, China.
Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, China.
Oncotarget. 2017 Jul 5;8(48):83660-83672. doi: 10.18632/oncotarget.19014. eCollection 2017 Oct 13.
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis. In contrast, cell proliferation was upregulated after inhibition of miR-33a-5p in WM35 cells, accompanied by increased glycolysis. Overexpression of miR-33a-5p enhanced the sensitivity of melanoma cells to X-radiation by MTT assay, while downregulation of miR-33a-5p had the opposite effects. Finally, experiments with xenografts in nude mice confirmed that high expression of miR-33a-5p in tumor cells increased radiosensitivity via inhibiting glycolysis. In conclusions, miR-33a-5p promotes radiosensitivity by negatively regulating glycolysis in melanoma.
据报道，糖酵解与放射抗性呈正相关。我们之前的研究发现，miR-33a通过靶向缺氧诱导因子1-α（已知可促进糖酵解的基因）在恶性黑色素瘤中发挥肿瘤抑制作用。然而，miR-33a-5p在放射敏感性中的作用仍有待阐明。我们发现miR-33a-5p在黑色素瘤组织和细胞中表达下调。在WM451细胞中过表达miR-33a-5p后，细胞增殖下调，同时糖酵解水平降低。相反，在WM35细胞中抑制miR-33a-5p后，细胞增殖上调，同时糖酵解增加。通过MTT试验，过表达miR-33a-5p增强了黑色素瘤细胞对X射线的敏感性，而miR-33a-5p的下调则产生相反的效果。最后，裸鼠异种移植实验证实，肿瘤细胞中miR-33a-5p的高表达通过抑制糖酵解增加了放射敏感性。总之，miR-33a-5p通过负向调节黑色素瘤中的糖酵解来促进放射敏感性。
