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.
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
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
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01 Jan 2014