miR-487a performs oncogenic functions in osteosarcoma by targeting BTG2 mRNA

Acta Biochim Biophys Sin (Shanghai). 2020 Jun 20;52(6):631-637. doi: 10.1093/abbs/gmaa034.

Abstract

Aberrant microRNA (miRNA) expression plays a critical role in osteosarcoma (OS) pathogenesis. In this study, we elucidated the involvement of miR-487a in OS and the underlying molecular mechanisms. We found that miR-487a was upregulated in OS clinical samples and cell lines. Knockdown of miR-487a suppressed OS cell growth and invasion and induced apoptosis; however, overexpression of miR-487a promoted OS cell growth and invasion. Accordingly, downregulation of miR-487a significantly suppressed tumor growth of OS xenografts in vivo. Furthermore, B-cell translocation gene 2 (BTG2) mRNA was found to be a novel target of miR-487a. Knockdown of BTG2 using small interfering RNA (siRNA) recapitulated the oncogenic effects of miR-487a, whereas BTG2 overexpression partially reversed these effects. Finally, miR-487a levels were found to be negatively correlated with BTG2 expression in OS clinical samples. Collectively, our data suggest that miR-487a is an oncogenic miRNA in OS and it lowers BTG2 expression.

Keywords: BTG2; invasion; miR-487a; osteosarcoma; proliferation.

MeSH terms

  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Humans
  • Immediate-Early Proteins / biosynthesis*
  • Immediate-Early Proteins / genetics
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oncogenes*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Immediate-Early Proteins
  • MIRN487 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • RNA, Neoplasm
  • Tumor Suppressor Proteins
  • BTG2 protein, human