siRNA targeting TCTP suppresses osteosarcoma cell growth and induces apoptosis in vitro and in vivo

Biotechnol Appl Biochem. 2016 Jan-Feb;63(1):5-14. doi: 10.1002/bab.1335. Epub 2015 Dec 22.

Abstract

Osteosarcoma (OS) remains the most frequent primary malignant bone tumor in adolescents. However, the molecular cause of the disease is poorly elucidated. In the present study, we primarily found that translationally controlled tumor protein (TCTP) was overexpressed in human OS tissues and cell lines. To investigate the function of TCTP in OS cell growth, an RNA interference lentivirus system was employed to deplete TCTP expression in Saos-2 and U2OS cell lines. Specific knockdown of TCTP significantly impaired cell proliferation and colony-formation capacity in both OS cell lines. Moreover, depletion of TCTP caused a significant accumulation of OS cells in the S phase and eventually induced cell apoptosis. Expression levels of the G2/M phase regulators cyclin B1 and Cdc25A were decreased, and apoptotic markers Bad and caspase-3 were increased in both OS cell lines after depletion of TCTP. Furthermore, depletion of TCTP potently inhibited the growth of xenografts in nude mice. Our results indicate that inhibition of TCTP expression exerts potential antitumor activity and may be a novel therapeutic approach in human OS.

Keywords: RNA interference; TCTP; apoptosis; osteosarcoma; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy*
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Cycle
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Nude
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / therapeutic use*
  • RNAi Therapeutics*
  • Tumor Protein, Translationally-Controlled 1

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • TPT1 protein, human
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1