miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways

Liu,Zhenlin; Jiang,Zhongmin; Huang,Jianyong; Huang,Shuqiang; Li,Yanxia; Yu,Simiao; Yu,Shizhu; Liu,Xiaozhi

doi:10.3892/ijo.2014.2322

miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways

Authors:
- Zhenlin Liu
- Zhongmin Jiang
- Jianyong Huang
- Shuqiang Huang
- Yanxia Li
- Simiao Yu
- Shizhu Yu
- Xiaozhi Liu
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Affiliations: Department of Neurosurgery, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China, Department of Pathology, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China, Department of Biomedical Engineering, Duke University, Durham, NC, USA, The Central Laboratory, The Fifth Central Hospital of Tianjin, Tianjin, P.R. China, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, P.R. China
Published online on: March 5, 2014 https://doi.org/10.3892/ijo.2014.2322
Pages: 1571-1580

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Abstract

Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3'-untranslated region (3'-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.

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