Overexpression of miR-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting SOX7

Clin Exp Med. 2017 Feb;17(1):51-58. doi: 10.1007/s10238-015-0398-6. Epub 2015 Oct 29.

Abstract

Osteosarcoma (OS) is one of the most common types of primary sarcoma of bone in children and young adults, and the long-term prognosis for OS patients still remains dismal due to the lack of effective early diagnostic biomarkers. Identifying sensitive and specific biomarkers in carcinogenesis may improve diagnostic and therapeutic strategies for this malignancy. The expression of miR-664 in osteosarcoma cell lines and osteosarcoma tissues was examined using real-time PCR. The effects of miR-664 on osteosarcoma cell migration and invasion were evaluated by cell invasion assays, migration assays, and three-dimension spheroid invasion assay. The effect of miR-664 on SOX7 was determined by luciferase assays and Western blot assay. The clinical association between miR-664 and SOX7 was analyzed by real-time PCR and Western blot assay. Expression of miR-664 was found to be upregulated in OS cell lines and tissues. Overexpression of miR-664 was associated with increased migration and invasive abilities of OS cells in vitro, whereas downregulation of miR-664 appeared to inhibit their migration and invasive potential. Furthermore, using biological approaches, we showed that miR-664 directly targeted and suppressed expression of the tumor suppressor SOX7. Additionally, the expression of miR-664 was negatively correlated with SOX7 expression in OS clinical tissues. Our findings suggest that miR-664 functions as an oncogene miRNA and has an important role in promoting human OS cell invasion and migration by suppressing SOX7 expression. Consequently, miR-664 may have potential as a novel diagnostic and therapeutic target of osteosarcoma.

Keywords: Invasion; Migration; Osteosarcoma; SOX7; miR-664.

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • SOXF Transcription Factors / genetics*
  • SOXF Transcription Factors / metabolism
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • MIRN664 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • SOX7 protein, human
  • SOXF Transcription Factors
  • Luciferases