Oncotarget

Research Papers:

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

Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng and Jianda Zhou _

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Oncotarget. 2017; 8:83660-83672. https://doi.org/10.18632/oncotarget.19014

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Abstract

Ke Cao1,*, Jingjing Li2,*, Jia Chen2,*, Li Qian3, Aijun Wang4, Xiang Chen5, Wei Xiong6, Jintian Tang7, Shijie Tang8, Yong Chen9, Yao Chen2, Yan Cheng10 and Jianda Zhou2

1Department of Oncology of Third Xiangya Hospital, Central South University, Changsha, China

2Department of Plastic Surgery of Third Xiangya Hospital, Central South University, Changsha, China

3Department of Burn and Plastic Surgery of Second Xiangya Hospital, Central South University, Changsha, China

4Surgical Bioengineering Laboratory, Department of Surgery, UC Davis School of Medicine, Sacramento, California, USA

5Department of Dermatology of Xiangya Hospital, Central South University, Changsha, China

6Cancer Research Institute, Key Laboratory of Carcinogenesis of Ministry of Health, Central South University, Changsha, China

7Institute of Medical Physics and Engineering, Department of Engineering Physics, Tsinghua University, Beijing, China

8Department of Plastic Surgery, Second Hospital of Shantou University, Shantou, China

9Key Laboratory of Genetics and Birth Health of Hunan Province, Family Planning Institute of Hunan Province, Changsha, China

10School of Pharmaceutical sciences, Central South University, Changsha, China

*These authors contributed equally to this work

Correspondence to:

Jianda Zhou, email: [email protected]

Yan Cheng, email: [email protected]

Yao Chen, email: [email protected]

Keywords: microRNA, radiation, glucose, HIF-1α, lactate dehydrogenase A

Received: January 10, 2017     Accepted: June 19, 2017     Published: July 05, 2017

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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