MicroRNA-379 suppresses osteosarcoma progression by targeting PDK1

J Cell Mol Med. 2017 Feb;21(2):315-323. doi: 10.1111/jcmm.12966. Epub 2016 Oct 25.

Abstract

Osteosarcoma is the most common primary bone tumour. Increasing evidence has demonstrated the pathogenic role of microRNA (miRNAs) dysregulation in tumour development. miR-379 was previously reported to function as an oncogenic or tumour-suppressing miRNA in a tissue-dependent manner. However, its function in osteosarcoma remains unknown. In this study, we found that the expression of miR-379 was downregulated in osteosarcoma tissues and cell lines. Further functional characterization revealed that miR-379 suppressed osteosarcoma cell proliferation and invasion in vitro and retarded the growth of osteosarcoma xenografts in vivo. Mechanistically, PDK1 was identified as the direct target of miR-379 in osteosarcoma, in which PDK1 expression was up-regulated and showed inverse correlation with miR-379. Enforced expression of PDK1 promoted osteosarcoma cell proliferation and rescued the anti-proliferative effect of miR-379. These data suggest that miR-379 could function as a tumour-suppressing miRNA via targeting PDK1 in osteosarcoma.

Keywords: PDK1; miR-379; microRNA; osteosarcoma.

MeSH terms

  • Adolescent
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Child
  • Disease Progression*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIRN379 microRNA, human
  • MicroRNAs
  • PDK1 protein, human
  • Pdk1 protein, mouse
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Protein Serine-Threonine Kinases