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miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma

Author

Listed:
  • Chuyong Lin

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

  • Aibin Liu

    (Zhongshan School of Medicine, Sun Yat-sen University)

  • Jinrong Zhu

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

  • Xin Zhang

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

  • Geyan Wu

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

  • Pengli Ren

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

  • Jueheng Wu

    (Zhongshan School of Medicine, Sun Yat-sen University)

  • Mengfeng Li

    (Zhongshan School of Medicine, Sun Yat-sen University)

  • Jun Li

    (Zhongshan School of Medicine, Sun Yat-sen University)

  • Libing Song

    (State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center)

Abstract

The strength and duration of phosphoinositide signalling from phosphatidylinositol-3-kinase (PI3K) activation to Akt is tightly balanced by phosphoinositide kinases and phosphatases. However, how phosphatase-mediated negative regulatory effects are concomitantly disrupted in cancers, which commonly exhibit constitutively activated PI3K/Akt signalling, remains undefined. Here we report that miR-508 directly suppresses multiple phosphatases, including inositol polyphosphate-5-phosphatase J (INPP5J), phosphatase and tensin homologue (PTEN) and inositol polyphosphate 4-phosphatase type I (INPP4A), resulting in constitutive activation of PI3K/Akt signalling. Furthermore, we find that overexpressing miR-508 promotes, while silencing miR-508 impairs, the aggressive phenotype of oesophageal squamous cell carcinoma (ESCC) both in vitro and in vivo. Importantly, the level of miR-508 correlates with poor survival and activated PI3K/Akt signalling in a large cohort of ESCC specimens. These findings uncover a mechanism for constitutive PI3K/Akt activation in ESCC, and support a functionally and clinically relevant epigenetic mechanism in cancer progression.

Suggested Citation

  • Chuyong Lin & Aibin Liu & Jinrong Zhu & Xin Zhang & Geyan Wu & Pengli Ren & Jueheng Wu & Mengfeng Li & Jun Li & Libing Song, 2014. "miR-508 sustains phosphoinositide signalling and promotes aggressive phenotype of oesophageal squamous cell carcinoma," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5620
    DOI: 10.1038/ncomms5620
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