MicroRNA-195-5p suppresses osteosarcoma cell proliferation and invasion by suppressing naked cuticle homolog 1

Cell Biol Int. 2017 Mar;41(3):287-295. doi: 10.1002/cbin.10723. Epub 2017 Jan 11.

Abstract

MiR-195-5p has been shown to play an essential role in human cancer progression. Nevertheless, the biological role of miR-195-5p in osteosarcoma development remains unclear. In this study, real-time PCR was performed to examine the miR-195-5p expression in human osteosarcoma cell lines. CCK-8 assay and Transwell assay were carried out to measure the effect of miR-195-5p on cell proliferation and invasion. Luciferase reporter assay was used to identify the targets of miR-195-5p. The results showed that miR-195-5p was significantly downregulated in osteosarcoma cells. Forced expression of miR-195-5p significantly inhibited cell proliferation, suppressed cell migration and invasion, compared with wild-type and control-transfected osteosarcoma cells. Luciferase reporter assay revealed that miR-195-5p binds to the 3'-untranslated region (UTR) of Naked cuticle homolog 1 (NKD1), indicating that NKD1 was a novel target of miR-195-5p. NKD1 mRNA and protein levels were reduced after overexpression of miR-195-5p. Moreover, silencing of NKD1 significantly inhibited the proliferation and invasion of osteosarcoma cells. Accordingly, our results support a tumor suppressor role of miR-195-5p in osteosarcoma through inhibiting NKD1, and it may be a promising therapeutic target for osteosarcoma.

Keywords: NKD1; miR-195-5p; osteosarcoma; therapeutic target; tumor growth; tumor suppressor.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Calcium-Binding Proteins
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology*
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Carrier Proteins
  • MIRN195 microRNA, human
  • MicroRNAs
  • NKD1 protein, human