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NeuroMolecular Medicine

, Volume 16, Issue 2, pp 517–528 | Cite as

miR-145 Inhibits Migration and Invasion of Glioma Stem Cells by Targeting ABCG2

  • Lei ShiEmail author
  • Zhimin Wang
  • Guan Sun
  • Yi Wan
  • Jun Guo
  • Xingli FuEmail author
Original Paper

Abstract

Despite advances in clinical therapies and technologies, the prognosis for patients with malignant glioma is poor. Our previous research demonstrated that glioma stem cells (GSCs) were crucial for glioma malignancy and accelerated tumor migration and invasion. The migration and invasion of malignant glioma cells into the surrounding normal brain tissues cause the poor outcome. miR-145, a miRNA found to be expressed in neurons, was recently found to have reduced expression in glioblastoma multiforme tumors. And miR-145 loss in glioma cells led to increased cell proliferation and invasion. However, its function on the migration and invasion of GSCs was still unknown. In this study, we aimed to identify the effects and mechanisms of miR-145 on the migration and invasion of GSCs. Our investigations revealed that miR-145 was low expressed in malignant glioma tissues and their corresponding GSCs. Knockdown of miR-145 in vitro could enhance the migration and invasion of GSCs, while up-regulation of miR-145 had the opposite effects. Further investigation of the potential mechanism demonstrated that the function of miR-145 in regulating the migration and invasion of GSCs is mediated by its targeting of ABCG2 mRNA. ABCG2 is an ATP-binding cassette transporter protein, which was identified to be overexpressed in GSCs and higher-grade glioma tissues. We found that miR-145 was negative correlated with ABCG2 levels in GSCs, and reduction in ABCG2 expression decreased the cell migration and invasion of GSCs. Further, a luciferase reporter proved that ABCG2 was a direct target of miR-145 in GSCs. Thus, these findings underscore the potential of miR-145 to regulate the migration and invasion of GSCs through targeting ABCG2.

Keywords

miR-145 Migration Invasion Glioma stem cells ABCG2 

Notes

Acknowledgments

This work was supported by the China Natural Science Foundation (81000963, 81370062, and 81302196), Jiangsu Province’s 333 Talent Program (BRA2011046), Jiangsu Province “six personnel peak” funded projects (2013-WSN-028), Jiangsu Province’s Natural Science Foundation (BK2012670), Medical Research Foundation by Jiangsu Province Health Department (YG201301 and Z201318), the Clinical Technology Development of Jiangsu University (JLY20120053), the Kunshan Social Development Foundation (KS1006, KS1009), and the Suzhou Social Development Foundation (SYS201063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

All authors have declared the sources of research funding for this manuscript and have no financial or other contractual agreements that might cause (or be perceived as causes of) conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe First People’s Hospital of Kunshan Affiliated with Jiangsu UniversitySuzhouPeople’s Republic of China
  2. 2.Department of NeurosurgerySuzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of MedicineSuzhouPeople’s Republic of China
  3. 3.Department of NeurosurgeryFourth Affiliated Yancheng Hospital of Nantong UniversityYanchengPeople’s Republic of China
  4. 4.Jiangsu University Health Science CenterZhenjiangPeople’s Republic of China

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