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

被引:40
作者
Cao, Ke [1 ]
Li, Jingjing [2 ]
Chen, Jia [2 ]
Qian, Li [3 ]
Wang, Aijun [4 ]
Chen, Xiang [5 ]
Xiong, Wei [6 ]
Tang, Jintian [7 ]
Tang, Shijie [8 ]
Chen, Yong [9 ]
Chen, Yao [2 ]
Cheng, Yan [10 ]
Zhou, Jianda [2 ]
机构
[1] Cent S Univ, Xiangya Hosp 3, Dept Oncol, Changsha, Hunan, Peoples R China
[2] Cent S Univ, Xiangya Hosp 3, Dept Plast Surg, Changsha, Hunan, Peoples R China
[3] Cent S Univ, Xiangya Hosp 2, Dept Burn & Plast Surg, Changsha, Hunan, Peoples R China
[4] UC Davis Sch Med, Dept Surg, Surg Bioengn Lab, Sacramento, CA USA
[5] Cent S Univ, Xiangya Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China
[6] Cent S Univ, Minist Hlth, Key Lab Carcinogenesis, Canc Res Inst, Changsha, Hunan, Peoples R China
[7] Tsinghua Univ, Inst Med Phys & Engn, Dept Engn Phys, Beijing, Peoples R China
[8] Shantou Univ, Hosp 2, Dept Plast Surg, Shantou, Peoples R China
[9] Family Planning Inst Hunan Prov, Key Lab Genet & Birth Hlth Hunan Prov, Changsha, Hunan, Peoples R China
[10] Cent S Univ, Sch Pharmaceut Sci, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA; radiation; glucose; HIF-1a; lactate dehydrogenase A; LUNG-CANCER CELLS; AEROBIC GLYCOLYSIS; NASOPHARYNGEAL CARCINOMA; INDUCED APOPTOSIS; BLADDER-CANCER; GASTRIC-CANCER; HYPOXIA; PROLIFERATION; METASTASIS; EXPRESSION;
D O I
10.18632/oncotarget.19014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:83660 / 83672
页数:13
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