| Author |
Duan, Hongyan Liu, Zhiyong Yang, Lifang Li, Dan Liu, Xiaowen Wu, Daobing Zhao, Ting Zhou, Shihua Xu, Shan |
| Description |
Author Affiliation: Liu X ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Duan H ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Zhou S ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Liu Z ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Wu D ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Zhao T ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.); Xu S ( Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China.); Yang L ( Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China.); Li D ( Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.) |
| Abstract |
microRNA (miR)-199a-3p serves critical roles in cancer development and progression. In order to improve knowledge of the functional mechanism of miR199a3p in testicular tumors, the present study characterized the regulation of aerobic glycolysis by miR199a3p and its impact on metabolism. Using 34,5dimethylthiazol2yl2,5 diphenyl tetrazolium bromide, wound healing and flow cytometry assays, it was determined that overexpression of miR199a3p in Ntera2 cells caused suppression of cell growth and migration. Further biochemical methods and highthroughput quantitative polymerase chain reaction array of metabolic genes showed that inhibition of miR199a3p markedly elevated lactate production and 12 differentially expressed genes, including 2 upregulated and 10 downregulated genes, were identified following treatment with miR199a3p in Ntera2 cells. In clinical samples, four selected genes, lactate dehydrogenase A, monocarboxylate transporter 1, phosphoglycerate kinase 1 and TP53inducible glycolysis and apoptosis regulator, were significantly overexpressed in malignant testicular germ cell tumor, and their expression inversely correlated with the expression of miR199a3p, suggesting that these four genes may be affected by miR199a3p. Using bioinformatics analysis, the transcription factor Sp1 binding site was identified in the promoter region of the four selected genes. In addition, miR199a3p was predicted to bind to conservative target sequences in the 3'untranslated region of Sp1 mRNA, suggesting that miR-199a-3p may downregulate these four metabolic genes through Sp1. It was demonstrated the dysregulated expression and activation of miR199a3p may serve important roles in aerobic glycolysis and tumorigenesis in patients with testicular cancer. Therefore, miR-199a-3p may be a potential biomarker in the prognosis and treatment of testicular tumors. |
