microRNA-33a-5p increases radiosensitivity by inhibiting glycolysis in melanoma.
microRNA-33a-5p increases radiosensitivity by inhibiting glycolysis in melanoma.
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microRNA-33a-5p 通过抑制黑色素瘤中的糖酵解来增加放射敏感性
DOI：
10.18632/oncotarget.19014
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发表时间：
2017-10-13
期刊：
影响因子：
--
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Cao K;Li J;Chen J;Qian L;Wang A;Chen X;Xiong W;Tang J;Tang S;Chen Y;Chen Y;Cheng Y;Zhou J
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 (HIF-1α)（一种已知促进糖酵解的基因），在恶性黑色素瘤中发挥肿瘤抑制因子的作用。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下调。 WM451 细胞中 miR-33a-5p 过表达后，细胞增殖下调，并伴有糖酵解水平降低。相反，在 WM35 细胞中抑制 miR-33a-5p 后，细胞增殖上调，并伴有糖酵解增加。 MTT检测显示，miR-33a-5p的过表达增强了黑色素瘤细胞对X射线的敏感性，而miR-33a-5p的下调则具有相反的作用。最后，裸鼠异种移植体内实验证实，肿瘤细胞中高表达的 miR-33a-5p 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。
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 (HIF-1α), 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, in vivo 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.