Cellular and Molecular Life Sciences

, Volume 67, Issue 12, pp 2069–2076 | Cite as

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

  • Shun He
  • Shangbin Yang
  • Guohua Deng
  • Mei Liu
  • Hongxia Zhu
  • Wei Zhang
  • Shuang Yan
  • Lanping Quan
  • Jinfeng Bai
  • Ningzhi Xu
Research Article

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.

Keywords

AURKA miR-17-92 E2F1 Transcription factor Tumorigenesis 

Notes

Acknowledgments

We thank Prof. Ashok R. Venkitaraman for kindly providing the pIRES-AURKA_KD-EGFP plasmid and Prof. Yu Zhang for the pGL3-6 × E2F-luciferase plasmid and E2F1 expression plasmid. This work was supported by National Natural Science Foundation (39925020, 30721001), National Basic Research Program (2004CB518701).

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Shun He
    • 1
  • Shangbin Yang
    • 1
  • Guohua Deng
    • 2
  • Mei Liu
    • 1
  • Hongxia Zhu
    • 1
  • Wei Zhang
    • 1
  • Shuang Yan
    • 1
  • Lanping Quan
    • 1
  • Jinfeng Bai
    • 1
  • Ningzhi Xu
    • 1
  1. 1.Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular OncologyCancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Department of PathologyCancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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