Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells

Cancer Sci. 2017 May;108(5):859-867. doi: 10.1111/cas.13201. Epub 2017 May 19.


Long non-coding RNA (lncRNA) have been the focus of increasing attention due to the role they play in many diseases, including osteosarcoma. The function of taurine upregulated gene 1 (TUG1) and its mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. In addition, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma. Moreover, we revealed that TUG1 and Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), a metastasis-related gene targeted by microRNA-335-5p (miR-335-5p), had the same miR-335-5p combining site. The subsequent luciferase assay verified TUG1 was a target of miR-335-5p. Furthermore, the results of a real-time quantitative PCR showed that TUG1 and miR-335-5p could affect each other's expression. respectively. Finally, we affirmed that TUG1 affected ROCK1 expression and ROCK1-mediated migration/invasion by working as a competitive endogenous RNA (ceRNA) via miR-335-5p. In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR-335-5p and ROCK1, and taking TUG1 as a new study point, provide new insight into molecular-level reversing migration and invasion of osteosarcoma.

Keywords: ceRNA; lncRNA TUG1; miR-335-5p; migration/invasion; osteosarcoma.

MeSH terms

  • Adolescent
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • RNA, Long Noncoding / genetics*
  • rho-Associated Kinases / genetics


  • MIRN335 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human
  • ROCK1 protein, human
  • rho-Associated Kinases