IGF1 3'UTR functions as a ceRNA in promoting angiogenesis by sponging miR-29 family in osteosarcoma

J Mol Histol. 2016 Apr;47(2):135-43. doi: 10.1007/s10735-016-9659-2. Epub 2016 Jan 12.

Abstract

Osteosarcoma is one of the most common malignant bone tumors in human worldwide. Angiogenesis is a pivotal process during osteosarcoma development. Insulin-like growth factor 1 (IGF1) has been reported to promote angiogenesis. However, the role of 3' untranslational region (3'UTR) of IGF1 mRNA in angiogenic activity in osteosarcomas is still unknown. In the present study, we performed gain-of-function assays to investigate the role of IGF1-3'UTR in angiogenesis. For the first time, we demonstrated that IGF1 3'UTR increased VEGF expression and promotes angiogenesis in osteosarcoma cells. In addition, RNA-immunoprecipitation and luciferase reporter assays showed that IGF1 3'UTR was a direct target of miR-29s. Our data also demonstrated that there existed a competition of miR-29s between IGF1-3'UTR and VEGF mRNA, and IGF1-3'UTR promoted angiogenesis at least in part via sponging miR-29s. Taken together, our study suggests that IGF1-3'UTR functions as a ceRNA in promoting angiogenesis by sponging miR-29s in osteosarcoma.

Keywords: Angiogenesis; IGF1; Osteosarcoma; VEGF; ceRNA; miR-29a; miR-29b; miR-29c.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Insulin-Like Growth Factor I / genetics*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Neovascularization, Pathologic / genetics*
  • Osteosarcoma / blood supply*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN29a microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I