MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1

Cancer Sci. 2010 Sep;101(9):1997-2004. doi: 10.1111/j.1349-7006.2010.01616.x.


MicroRNAs (miRNAs) are frequently deregulated in human tumors, and play important roles in tumor development and progression. The pathological roles of miRNAs in neurofibromatosis type 1 (NF1) tumorigenesis are largely unknown. We demonstrated that miR-10b was up-regulated in primary Schwann cells isolated from NF1 neurofibromas and in cell lines and tumor tissues from malignant peripheral nerve sheath tumors (MPNSTs). Intriguingly, a significantly high level of miR-10b correlated with low neurofibromin expression was found in a neuroectodermal cell line: Ewing's sarcoma SK-ES-1 cells. Antisense inhibiting miR-10b in NF1 MPNST cells reduced cell proliferation, migration and invasion. Furthermore, we showed that NF1 mRNA was the target for miR-10b. Overexpression of miR-10b in 293T cells suppressed neurofibromin expression and activated RAS signaling. Antisense inhibition of miR-10b restored neurofibromin expression in SK-ES-1 cells, and decreased RAS signaling independent of neurofibromin in NF1 MPNST cells. These results suggest that miR-10b may play an important role in NF1 tumorigenesis through targeting neurofibromin and RAS signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • Neurofibromatosis 1 / genetics*
  • Neurofibromatosis 1 / metabolism
  • Neurofibromatosis 1 / pathology
  • Neurofibromin 1 / genetics
  • Neurofibromin 1 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • RNA, Antisense / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Signal Transduction*
  • Tumor Cells, Cultured
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • 3' Untranslated Regions
  • MIRN10 microRNA, human
  • MicroRNAs
  • Neurofibromin 1
  • RNA, Antisense
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins