title: Overexpression of DCF1 inhibits glioma through destruction of mitochondria and activation of apoptosis pathway.
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.
authors.affiliation: 1] Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China [2] Institute of Systems Biology, Shanghai University, Shanghai 200444, China [3].
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: 1] Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China [2] Institute of Systems Biology, Shanghai University, Shanghai 200444, China [3].
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Yang
authors.affiliation: 1] Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China [2] Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
authors.forename: Liucun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Yan
authors.affiliation: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Feng
authors.affiliation: 1] Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China [2] Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
authors.forename: Zengrong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1] Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai 200444, China [2] Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
authors.forename: Tieqiao
authors.initials: T
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D053148:Caspase 3