科研之友
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摘要
microRNA (miR)-199a-3p serves critical roles in cancer development and progression. In order to improve knowledge of the functional mechanism of miR-199a-3p in testicular tumors, the present study characterized the regulation of aerobic glycolysis by miR-199a-3p and its impact on metabolism. Using 3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide, wound healing and flow cytometry assays, it was determined that overexpression of miR-199a-3p in Ntera-2 cells caused suppression of cell growth and migration. Further biochemical methods and high-throughput quantitative polymerase chain reaction array of metabolic genes showed that inhibition of miR-199a-3p markedly elevated lactate production and 12 differentially expressed genes, including 2 upregulated and 10 downregulated genes, were identified following treatment with miR-199a-3p in Ntera-2 cells. In clinical samples, four selected genes, lactate dehydrogenase A, monocarboxylate transporter 1, phosphoglycerate kinase 1 and TP53-inducible glycolysis and apoptosis regulator, were significantly overexpressed in malignant testicular germ cell tumor, and their expression inversely correlated with the expression of miR-199a-3p, suggesting that these four genes may be affected by miR-199a-3p. Using bioinformatics analysis, the transcription factor Sp1 binding site was identified in the promoter region of the four selected genes. In addition, miR-199a-3p 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 miR-199a-3p 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.
