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MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1

  • Research Article
  • Published:
Tumor Biology

Abstract

The aberrant expression of microRNAs (miRNAs) is always associated with tumor development and progression. Microvascular proliferation is one of the unique pathologic features of glioblastoma (GBM) . In this study, the microvasculature from GBM or normal brain tissue derived from neurosurgeries was purified and total RNA was isolated from purified microvasculature. The difference of miRNA expression profiles between glioblastoma microvasculature and normal brain capillaries was investigated. It was found that miR-7-5p in GBM microvessels was significantly reduced compared with that in normal brain capillaries. In the in vitro experiments, overexpression of miR-7-5p significantly inhibited human umbilical vein endothelial cell proliferation. Forced expression of miR-7-5p in human umbilical vein endothelial cells in vitro significantly reduced the protein level of RAF1 and repressed the activity of the luciferase, a reporter vector carrying the 3′-untranslated region of RAF1. These findings indicate that RAF1 is one of the miR-7-5p target genes. Furthermore, a significant inverse correlation between miR-7-5p expression and RAF1 protein level in GBM microvasculature was found. These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate GBM microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, implicating an important role for miR-7-5p in the pathogenesis of GBM. It may serve as a guide for the antitumor angiogenesis drug development.

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Abbreviations

MiRNA:

MicroRNA

GBM:

Glioblastoma

qRT-PCR:

Real-time quantitative reverse transcriptase PCR

3′-UTR:

3′-Untranslated region

WT:

Wild type

MUT:

Mutant type

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Acknowledgments

We thank Yan Song, Meng Zhang, and Yubao Zhang for the administrative and operational support; Drs. Guiyan Xu, Guangming Qu, Deze Jia, and Donghai Wang for their helpful discussions and critical reading of the manuscript.

Ethics approval

Ethics approval was provided by the National Hospital for Neurology and Neurosurgery Research Ethics Committee.

Conflicts of interest

None, there are no conflict of interest.

Funding

This work was supported by the National Natural Scientific Foundation of China (NO.81141088) and by the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province. (NO. 2004BS02010). JYL was supported by North Shore-LIJ Cancer Institute.

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Authors and Affiliations

  1. Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong, People’s Republic of China

    Zhiguo Liu, Yuguang Liu, Lianling Li, Zhenkuan Xu, Baibin Bi & Yunyan Wang

  2. Department of Pathology and Laboratory Medicine, North Shore-Long Island Jewish Health System, Lake Success, Hofstra North Shore-LIJ School of Medicine, New York, NY, USA

    Jian Yi Li

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  1. Zhiguo Liu
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  2. Yuguang Liu
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  3. Lianling Li
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  4. Zhenkuan Xu
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Correspondence to Yunyan Wang.

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Liu, Z., Liu, Y., Li, L. et al. MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1. Tumor Biol. 35, 10177–10184 (2014). https://doi.org/10.1007/s13277-014-2318-x

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  • DOI: https://doi.org/10.1007/s13277-014-2318-x

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