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Downregulation of AIF-2 Inhibits Proliferation, Migration, and Invasion of Human Glioma Cells via Mitochondrial Dysfunction

  • Wei ChenEmail author
  • Hao Liu
  • Tuo Wang
  • Gang Bao
  • Ning Wang
  • Rui-Chun Li
Article

Abstract

Glioma remains the leading cause of brain tumor–related death worldwide. Apoptosis inducing factor (AIF) is a family of mitochondrial oxidoreductases that play important roles in mitochondrial metabolism and redox control. AIF-1 has been demonstrated to exert cell-killing effect via apoptosis in cancer cells, whereas the role of AIF-2 in cancer cells has not been determined. This study aimed to investigate the role of AIF-2 in human glioma cells. We found that AIF-2 was upregulated in human glioma tissues and cell lines, especially in U251 cells. Downregulation of AIF-2 using specific siRNA (Si-AIF-2) significantly reduced cell proliferation, induced G1 cell cycle arrest and differently regulated the expression of cell cycle regulator proteins in U251 cells. In addition, the results of Matrigel invasion assay and live-cell tracking assay showed that knockdown of AIF-2 inhibited cell invasion and migration. The results of immunocytochemistry indicated that knockdown of AIF-2 significantly attenuated the nuclear translocation of AIF-1, which was confirmed by western blot analysis. Furthermore, downregulation of AIF-2 resulted in mitochondrial dysfunction in U251 cells, as evidenced by reduced mitochondrial membrane potential (MMP), mitochondrial complex I activity, and mitochondrial Ca2+ buffering capacity. In conclusion, we found that AIF-2 plays a key role in promoting cell proliferation, invasion, and migration via regulating AIF-1-related mitochondrial cascades. Downregulation of the candidate oncogene AIF-2 might constitute a strategy to kill human glioma cells.

Keywords

Glioma AIF Mitochondrial dysfunction Apoptosis 

Notes

Acknowledgements

The authors would like to thank Dr. Terry Chen for his technical support for the experiments and the preparation of the manuscript.

Compliance with Ethical Standards

This study was approved by the Human Research Ethics Committee of Xi’an Jiaotong University.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

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