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.

Dynamin-related protein 1 controls the migration and neuronal differentiation of subventricular zone-derived neural progenitor cells

“…Several lines of evidence suggest that mitochondria may regulate NSC differentiation. For instance, overexpression of the dcf1 gene caused mitochondria destruction and activated the apoptosis pathway 39 . It was shown earlier that silencing dcf1 altered NSC differentiation, leading to greater differentiation into astrocytes 40 .…”

TMEM59 potentiates Wnt signaling by promoting signalosome formation

“…Although we show that TMEM59 expression also diminishes glycan modification of FZD, we were unable to link these glycosylation alterations to the Wnt-potentiating activity of TMEM59. In addition, TMEM59 was reported to induce unconventional autophagy in response to bacterial infection and to promote apoptotic cell death in neuronal cells ( 47 , 55 , 56 ). Both these functions require the TMEM59 intracellular domain that is dispensable for its role in Wnt signaling.…”

CRM197 in Combination With shRNA Interference of VCAM-1 Displays Enhanced Inhibitory Effects on Human Glioblastoma Cells

“…Apoptosis is mediated by caspases, which are cysteine proteases that cleave target proteins at aspartic acid (Kim et al, 2013). In the present study, we investigated the influence of CRM197 and shRNA-VCAM-1 on the activation of caspase-3, 8, and 9, which contribute most in the apoptosis of glioma cells (Wang et al, 2013b;Guo et al, 2014;Xie et al, 2014). Caspase-3 is a common proteolytic enzyme involved in both the extrinsic and intrinsic apoptotic pathways (Wang et al, 2013c).…”