title: miR-26b inhibits proliferation, migration, invasion and apoptosis induction via the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 driven glycolysis in osteosarcoma cells.
abstract: MicroRNAs (miRNAs) are differentially expressed and play crucial roles in cancer development and progression. Elevated glycolysis provides survival advantage and metastatic phenotype. Emerging evidence indicates that glycolysis in cancers can be regulated by miRNAs. In the present study, the role of miR-26b in the proliferation, invasion and glycolytic phenotype of osteosarcoma (OS) cells was investigated. miR-26b was reported to be downregulated in OS tissues, however, the effect of miR-26b on OS has not been distinctly evaluated. The present study therefore investigated the miR-26b sensitivity mechanism in OS. To determine the role of miR-26, we reinstated its expression in the U2OS OS cell line through transfection with miR-26b mimics and examined the effects on cell proliferation, migration, invasion, cell cycle progression and glycolytic parameters. The computational prediction tool was employed to identify the molecular target of miR-26b and was confirmed experimentally. Restoration of miR-26b expression inhibited cell proliferation, migration and invasion, arrested cell cycle progression, and induced cell apoptosis accompanied by the downregulation of glycolytic phenotype. Moreover, the binding site for miR-26b was predicted in the 3'UTR of gene 6-phosphofructo-2-kinase/fructose‑2,6-bisphosphatase-3 (PFKFB3), suggesting a role for miR-26b in metabolic alteration in OS cells. Further studies showed that overexpression of miR-26b repressed PFKFB3 mRNA and protein levels followed by modulation of the expression of glycolytic components (LDHA, GLUT-1) and markers of invasion and cell cycle such as MMP-9, MMP-2, cyclin D1 and p27. Collectively, the data suggested the tumor suppressive role of miR-26b which functions by targeting the glycolytic metabolism in OS cells, and providing a possible therapeutic strategy for OS patients by targeting miRNA expression.
authors: Department of Orthopedics, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Jing-Yu
authors: JY
authors: Du
authors: Department of Orthopedics, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Li-Feng
authors: LF
authors: Wang
authors: Department of Orthopedics, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Quan
authors: Q
authors: Wang
authors: Department of Orthopedics, The First Affiliated Hospital of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
authors: Lie-Dao
authors: LD
authors: Yu
mesh_terms: D017209:Apoptosis; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D004734:Energy Metabolism; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D025481:Phosphofructokinase-2 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D025481:Phosphofructokinase-2; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C528163:MIRN26 microRNA, human; C107345:PFKFB3 protein, human