MicroRNA-100 suppresses human osteosarcoma cell proliferation and chemo-resistance via ZNRF2

Oncotarget. 2017 May 23;8(21):34678-34686. doi: 10.18632/oncotarget.16149.


Osteosarcoma (OS) is a prevalent cancer worldwide. MicroRNAs (miRNAs) play critical roles in the growth, invasion and carcinogenesis of OS, whereas the underlying mechanisms remain ill-defined. Here, we addressed these questions. We detected significantly higher levels of ZNRF2, a ubiquitin ligase of the RING superfamily, and significantly lower levels of miR-100 in the OS specimens, compared to the paired normal bone tissues. The levels of ZNRF2 and miR-100 inversely correlated in the OS specimens. In addition, low miR-100 levels are associated with poor prognosis of the OS patients. Either ZNRF2 overexpression or miR-100 depletion increased in vitro OS cell growth and improved cell survival at the presence of Doxorubicin. Mechanistically, with the help of bioinformatics analysis and luciferase-reporter assay, we found that miR-100 might bind to the 3'-UTR of ZNRF2 mRNA to prevent its protein translation. Thus, our data suggest that re-expression of miR-100 may inhibit OS cell growth and decrease OS cell chemo-resistance.

Keywords: ZNRF2; cancer growth; chemo-resistance; miR-100; osteosarcoma (OS).

MeSH terms

  • 3' Untranslated Regions
  • Bone Neoplasms / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Osteosarcoma / genetics*
  • Prognosis
  • Survival Analysis
  • Ubiquitin-Protein Ligases / genetics*


  • 3' Untranslated Regions
  • MIRN100 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • Ubiquitin-Protein Ligases
  • ZNRF2 protein, human