Upregulated miR-221/222 promotes cell proliferation and invasion and is associated with invasive features in retinoblastoma

Cancer Biomark. 2018;22(4):621-629. doi: 10.3233/CBM-170721.

Abstract

Background and objectives: MicroRNA (miR-221/222) is frequently overexpressed in many cancers and is associated with poor prognosis. However, the role of miR-221/222 in retinoblastoma (RB) remains unclear. This study aimed to detect the clinical significance of miR-221/222 in RB patients and explore its role in RB cells in vitro.

Methods: Expression of miR-221/222 was assessed in fresh RB tissue collected from 64 eyes and normal retinal tissues from 18 unrelated donor cadaver eyes by quantitative real time RT-PCR analysis (qRT-PCR), and correlated with the histopathological findings. Human RB Y79 cells were transfected with miR-221/222 precursors or inhibitors to overexpress or downregulate miR-221/222 expression, respectively, using Lipofectamine 2000 reagent. The biological effects of miR-221/222 were then assessed by cell viability assays, colony formation assays, apoptosis detection assays, Matrigel® invasion assays, and wound-healing assays.

Results: Higher miR-221/222 expression was detected in RB tissues compared to that of the normal retinal tissues (p< 0.001). Higher miR-221/222 expression was correlated with invasion in patients with RB. Targeting of miR-221/222 induced apoptosis and inhibited Y79 cell proliferation, migration, and invasion in vitro. However, overexpression of miR-221/222 promoted Y79 cell proliferation, migration, and invasion in vitro.

Conclusions: Overexpression of miR-221/222 was associated with tumor invasiveness in patients with RB. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice.

Keywords: Retinoblastoma; invasion; marker; miR-221/222.

MeSH terms

  • Apoptosis / genetics
  • Cadaver
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Retinoblastoma / genetics*
  • Retinoblastoma / pathology
  • Retinoblastoma / surgery
  • Tissue Donors

Substances

  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs