4.3 Article

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

期刊

ONCOTARGET
卷 8, 期 48, 页码 83660-83672

出版社

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19014

关键词

microRNA; radiation; glucose; HIF-1a; lactate dehydrogenase A

资金

  1. National Natural Science Foundation of China [81572689, 81372140, 81301688, 81272192, 81572965]
  2. Program for New Century Excellent Talents in University [NCET-11-0527]
  3. Natural Science Foundation of Hunan Province [2016JJ6154]
  4. Project of the Department of Science and Technology of Hunan Province [2015SK2066, 2014SK2018, 2013FJ6003]
  5. 125 Talent Project/New xiangya project of the Third Xiangya Hospital of Central South University
  6. Fundamental Research Funds for the Central Universities of Central South University [2017zzts220]

向作者/读者索取更多资源

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-1a), 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 miR33-a-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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