Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma

Oncogene. 2015 Mar 26;34(13):1619-1628. doi: 10.1038/onc.2014.98. Epub 2014 Apr 21.


MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 6 / analysis
  • ErbB Receptors / analysis
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Glioblastoma / pathology*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / analysis
  • Male
  • Mice
  • MicroRNAs / analysis
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • bcl-X Protein / analysis


  • Insulin-Like Growth Factor Binding Protein 2
  • MIRN491 microRNA, human
  • MicroRNAs
  • bcl-X Protein
  • ErbB Receptors
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6