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microRNA-33a-5p increases radiosensitivity by inhibiting glycolysis in melanoma.

  • Author(s): 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
  • et al.
Abstract

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.

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