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

Authors
  • Chen, Wei1
  • Liu, Hao1
  • Wang, Tuo1
  • Bao, Gang1
  • Wang, Ning1
  • Li, Rui-Chun1
  • 1 The First Affiliated Hospital of Xi’an Jiaotong University, Department of Neurosurgery, Xi’an, Shaanxi, 710061, China , Xi’an (China)
Type
Published Article
Journal
Journal of Molecular Neuroscience
Publisher
Springer-Verlag
Publication Date
Apr 13, 2019
Volume
68
Issue
2
Pages
304–310
Identifiers
DOI: 10.1007/s12031-019-01306-y
Source
Springer Nature
Keywords
License
Yellow

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.

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