miR-22 inhibits the proliferation, motility, and invasion of human glioblastoma cells by directly targeting SIRT1

Tumour Biol. 2016 May;37(5):6761-8. doi: 10.1007/s13277-015-4575-8. Epub 2015 Dec 10.

Abstract

Recently, microRNAs (miRNAs), a kind of small and non-coding RNA, can target the downstream molecules. Increasing evidence demonstrates that miRNAs meditate the onset and progression of a variety of tumors. In the present study, we carried out gene transfection, western blot, and reverse transcription PCR (RT-PCR) to explore the role of miR-22 in glioblastoma tissues and cell lines. Here, we verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte (NHA) cells (p < 0.001). By contrast, SIRT1 messenger RNA (mRNA) and protein were upregulated in glioblastoma tissues and cells (p < 0.001). In vitro miR-22 mimics interfered with cell proliferation, migration, and invasion of U87 and U251 cells. Mechanically, the 3'-untranslated regions (3'-UTRs) of SIRT1 were a direct target of miR-22, leading to the decreased expression of SIRT1 protein in U87 and U251 cells. Meanwhile, miR-22 mimics also inhibited the expression of epidermal growth factor receptor (EGFR) and matrix metallopeptidase 9 (MMP9). In conclusion, miR-22 inhibited cell proliferation, migration, and invasion via targeting the 3'-UTR of SIRT1 in the progression of glioblastoma and miR-22-SIRT1 pathway can be recommended as a potential target for treatment of glioblastoma.

Keywords: Glioblastoma; SIRT1; miR-22.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • RNA Interference*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Sirtuin 1 / chemistry
  • Sirtuin 1 / genetics*
  • Transcriptome

Substances

  • 3' Untranslated Regions
  • MIRN22 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Sirtuin 1