title: Let-7g reverses malignant phenotype of osteosarcoma cells by targeting Aurora-B.
abstract: Accumulating studies revealed that the expression levels of several miRNAs are up or down-regulated in osteosarcoma (OS). The aim of this study was to investigate the functional significance and molecular of the let-7g in OS cells. The expression levels of let-7g was significantly down-regulated in OS cell lines U2-OS and HOS cell compared to osteoblast cell lines HOB cell. Moreover, bioinformatic prediction suggested that Aurora-B, which is overexpressed and functions as an oncogene in OS cells, is a putative target gene of let-7g. Using mRNA and protein expression analysis and luciferase assays, we further identified let-7g directly regulated Aurora-B expression in OS cells. Functional investigation revealed both restoration of let-7g and silencing Aurora-B induce cell apoptosis and suppressed cell viability, migratory and invasive ability in OS cells. Finally, we found that silencing Aurora-B in OS cells could partly dampen anti-let-7g mediated tumor promotion. Thus, our findings suggested that let-7g inhibits OS cell malignant phenotype at least partly through targeting Aurora-B. Targeting of let-7g and Aurora-B may be a novel therapeutic strategy for treating OS.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Jia Ming
authors.initials: JM
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Long
authors.affiliation: Department of Orthopedics, The Second Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Guo Mei
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Xuan Yin
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Shan Hu
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Zhi Li
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanchang University Jiangxi, China.
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D064107:Aurora Kinase B / Q000096:biosynthesis*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: Aurora-B; Osteosarcoma; let-7; metastasis