title: microRNA-199a-3p functions as tumor suppressor by regulating glucose metabolism in testicular germ cell tumors.
abstract: 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.
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Duan
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Daobing
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Life Science, College of Biology, Hunan University, Changsha, Hunan 410082, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D016329:Sp1 Transcription Factor; C531408:mirn199 microRNA, human; D019344:Lactic Acid; D005947:Glucose