Let-7g reverses malignant phenotype of osteosarcoma cells by targeting Aurora-B

Int J Clin Exp Pathol. 2014 Jul 15;7(8):4596-606. eCollection 2014.

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.

Keywords: Aurora-B; Osteosarcoma; let-7; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Aurora Kinase B / biosynthesis*
  • Blotting, Western
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Computational Biology
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Phenotype
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • MicroRNAs
  • mirnlet7 microRNA, human
  • AURKB protein, human
  • Aurora Kinase B