Aurora kinase A induces miR-17-92 cluster through regulation of E2F1 transcription factor

Cell Mol Life Sci. 2010 Jun;67(12):2069-76. doi: 10.1007/s00018-010-0340-8. Epub 2010 Mar 19.

Abstract

Aurora kinase A (AURKA) is an essential mitotic serine/threonine kinase and its abnormal expression is observed in many malignancies, yet the exact role for AURKA in tumorigenesis still remains elusive. Here, through a transcription factor array, we show that the transcription activity of E2F1 was increased by AURKA overexpression. Meanwhile, the E2F1 protein level was found to be upregulated and a correlation between AURKA and E2F1 expression was observed in cancer specimens. Further analysis revealed that AURKA increased E2F1 protein stability by inhibiting proteasome-dependent degradation of this protein. Additionally, a microRNA cluster, miR-17-92, was found to be upregulated upon AURKA overexpression, and this stimulation was largely repressed by E2F1 knockdown. Chromatin immunoprecipitation further demonstrated that AURKA enhanced E2F1 occupancy to the promoter of the miR-17-92 cluster. These data reveal a novel link between AURKA and microRNAs via the regulation of E2F1, providing new clues for understanding the role of AURKA in tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A
  • Aurora Kinases
  • Chromatin Immunoprecipitation
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • E2F1 Transcription Factor / physiology*
  • Humans
  • MicroRNAs / genetics*
  • Phosphotransferases / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Regulatory Sequences, Nucleic Acid / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MicroRNAs
  • Transcription Factors
  • Phosphotransferases
  • AURKA protein, human
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases