P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2

Neurosci Lett. 2013 Feb 8:534:327-32. doi: 10.1016/j.neulet.2012.11.047. Epub 2012 Dec 7.

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that function as tumor suppressors or oncogenes. MicroRNA-107 (miR-107), a transcriptional target of p53, is deregulated in many cancer cell lines. Here, we showed that miR-107 is down-regulated in glioma tissues and cell lines, in particular, p53-mutated U251 and A172. Transfection of wild-type p53 into these cells stimulated miR-107 expression. To investigate the role of miR-107 in tumorigenesis, we constructed a lentiviral vector overexpressing miR-107. Notably, miR-107 inhibited proliferation and arrested the cell cycle at the G0-G1 phase in glioma cells. Transduction of Lenti-GFP-miR-107 into glioma cells inhibited CDK6 and Notch-2 protein expression. Our findings collectively demonstrate that p53-induced miR-107 suppresses brain tumor cell growth and down-regulates CDK6 and Notch-2 expression, supporting its tumor suppressor role and utility as a target for glioma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase 6 / biosynthesis*
  • Down-Regulation
  • Glioma
  • Humans
  • Lentivirus / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Receptor, Notch2 / biosynthesis*
  • Transduction, Genetic
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • MIRN107 microRNA, human
  • MicroRNAs
  • NOTCH2 protein, human
  • Receptor, Notch2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6