MicroRNA-490-3p regulates cell proliferation and apoptosis by targeting HMGA2 in osteosarcoma

FEBS Lett. 2015 Oct 7;589(20 Pt B):3148-53. doi: 10.1016/j.febslet.2015.08.034. Epub 2015 Sep 1.

Abstract

MicroRNA-490-3p (miR-490-3p) has been implicated in several human malignancies; however, its potential functions and the underlying molecular mechanisms in osteosarcoma progression remain largely unclear. Here, we showed that miR-490-3p was down-regulated in osteosarcoma cell lines. Ectopic expression of miR-490-3p decreased cell proliferation, induced G1 arrest and apoptosis in vitro and inhibited tumorigenicity in a mouse xenograft model. Furthermore, miR-490-3p bound directly to HMGA2 mRNA 3'UTR and mediated a decrease in HMGA2 mRNA and protein expression. Re-expression of HMGA2 reversed the inhibitory effects of miR-490-3p. Further investigations showed an inverse correlation between low miR-490-3p and high HMGA2 expression in osteosarcoma tissues. Taken together, our results suggest that miR-490-3p functions as a potential tumor suppressor by down-regulating HMGA2 expression directly, and it may represent a potential therapeutic target for patients with osteosarcoma.

Keywords: High mobility group a isoform 2; MicroRNA-490-3p; Osteosarcoma; Proliferation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HMGA2 Protein / genetics*
  • HMGA2 Protein / metabolism
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Mutation
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Transplantation, Heterologous

Substances

  • 3' Untranslated Regions
  • HMGA2 Protein
  • MIRN490 microRNA, human
  • MicroRNAs