title: MicroRNA-124 upregulation inhibits proliferation and invasion of osteosarcoma cells by targeting sphingosine kinase 1.
abstract: Increasing evidence has confirmed that the dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studies have shown that the dysregulation of miR-124 is in numerous cancers. However, the roles of miR-124 in human osteosarcoma (OS) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-124 in OS cell lines, discussing whether it could be a therapeutic biomarker of OS in the future. In this study, our results demonstrated that miR-124 was down-regulated in OS cell lines and tissues. Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and tissues. Up-regulation of miR-124 significantly inhibited cell proliferation, invasion, and MMP-2 and -9 expressions of OS cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-124. Further study by luciferase reporter assay demonstrated that miR-124 could directly target SPHK1. Overexpression of SPHK1 in OS cells transfected with miR-124 mimic partially reversed the inhibitory of miR-124. In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.
authors.affiliation: Affiliated Hospital, College of Medicine, Hebei University of Engineering, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of General Surgery V, Affiliated Hospital of Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China. hanyanzhenhebei@163.com.
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Han
authors.affiliation: Laboratory Medicine, Sixth Hospital of Handan, Handan, 056000, Hebei, People's Republic of China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery V, Affiliated Hospital of Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of General Surgery V, Affiliated Hospital of Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of General Surgery V, Affiliated Hospital of Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery V, Affiliated Hospital of Hebei University of Engineering, Congtai Road No. 81, Handan, 056002, Hebei, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Jia
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics* / Q000502:physiology*; D000099157:Sphingosine Kinase
chemical_list: D035683:MicroRNAs; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C509207:MIRN124 microRNA, human
keywords: Invasion; MicroRNA-124; Osteosarcoma; Proliferation; Sphingosine kinase 1