Down-regulation of ribosomal protein S15A inhibits proliferation of human glioblastoma cells in vivo and in vitro via AKT pathway

Tumour Biol. 2016 Apr;37(4):4979-90. doi: 10.1007/s13277-015-4323-0. Epub 2015 Nov 4.

Abstract

Ribosomal protein s15a (RPS15A), a highly conserved cytoplasmic protein, promotes mRNA/ribosome interaction in translation. Recent evidence showed that RPS15A is essential for tumor growth. RPS15A expression level was measured in glioblastoma tissue samples and normal brain (NB) tissue samples. RPS15A RNAi stable cell line U87 and U251 was generated by the pLVTHM-GFP lentiviral RNAi expression system. The knockdown efficiency was confirmed by quantitative real-time PCR and western blot. Molecular mechanisms and the effect of RPS15A on cell growth and migration were investigated by using western blot, MTT assay, wound healing assay, transwell migration assay, and tumorigenesis in nude mice. Here, we report that RPS15A is overexpressed in human glioblastoma tumor tissues. RPS15A knockdown inhibits proliferation and migration of glioblastoma cells in vitro. Knocking down RPS15A leads to the level of p-Akt decrease and cell cycle arrested in G0/G1 phase in U87 and U251 cells. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice is inhibited by transduction with Lv-shRPS15A. Our findings indicate that RPS15A promotes cell proliferation and migration in glioblastoma for the first time. RPS15A might play a distinct role in glioblastoma and serve as a potential target for therapy.

Keywords: AKT pathway; Glioblastoma; Glioma; RPS15A; Therapy.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Lentivirus / genetics
  • Male
  • Mice
  • Middle Aged
  • Oncogene Protein v-akt / genetics*
  • RNA Interference
  • RNA, Messenger / biosynthesis
  • Ribosomal Proteins / biosynthesis*
  • Ribosomal Proteins / genetics
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • RNA, Messenger
  • Ribosomal Proteins
  • ribosomal protein S15a
  • Oncogene Protein v-akt