Abstract
Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To decode the apoptosis induced by dcf1, mitochondrial structure and membrane potential in glioma cells were investigated and the results indicated obvious mitochondrial swelling, destruction of cristae, and a significant decline in membrane potential. Mechanismly, caspase-3 signaling was activated. Finally, endogenous dcf1 silence in U251 cells was investigated. Results showed a highly methylation at -1339 and -1322 position at dcf1 promoter sequence, revealing the causal relationship between dcf1 gene and tumorigencicity. The present study identified a previously unknown cancer apoptosis mechanism involving dcf1 overexpression and provided a novel approach to potentially treat glioma patients.
Recommended Citation
Y. Xie et al., "Overexpression of DCF1 Inhibits Glioma through Destruction of Mitochondria and Activation of Apoptosis Pathway," Scientific Reports, vol. 4, Nature Research, Jan 2014.
The definitive version is available at https://doi.org/10.1038/srep03702
Department(s)
Electrical and Computer Engineering
Keywords and Phrases
Apoptosis Regulatory Protein; Caspase 3; Membrane Protein, Animal; Apoptosis; Brain Tumor; Cell Differentiation; Cell Line; Cell Proliferation; Genetics; Glioma; HEK293 Cell Line; Human; Mitochondrial Membrane Potential; Mitochondrion; Mouse; Nude Mouse; Pathology; Promoter Region; Tumor Cell Line, Animals; Apoptosis; Apoptosis Regulatory Proteins; Brain Neoplasms; Caspase 3; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Glioma; HEK293 Cells; Humans; Membrane Potential, Mitochondrial; Membrane Proteins; Mice; Mice, Nude; Mitochondria; Promoter Regions, Genetic
International Standard Serial Number (ISSN)
2045-2322
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2014 The Authors, All rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution 4.0 License.
Publication Date
01 Jan 2014
PubMed ID
24424470
Comments
This work was supported by the National Natural Science Foundation of China (Grant No 31070954, 81271253,11172158), the Key Innovation Project of Shanghai Municipal Education Commission (Grant No. 14ZZ090) and in part by the First-class Discipline of Universities in Shanghai.