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Upregulation of the checkpoint protein CHFR is associated with tumor suppression in pancreatic cancers

The checkpoint with forkhead-associated (FHA) domain and RING-finger (CHFR) protein was identified as a cell cycle checkpoint protein and E3 ubiquitin ligase. In the present study, the potential functions of CHFR in pancreatic cancer were investigated. CHFR expression was measured in five pancreatic...

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Detalles Bibliográficos
Autores principales: Zhang, Di, Xu, Xiao-Lan, Li, Fei, Sun, Hai-Chen, Cui, Ye-Qing, Liu, Shuang, Xu, Ping-Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755226/
https://www.ncbi.nlm.nih.gov/pubmed/29344247
http://dx.doi.org/10.3892/ol.2017.7239
Descripción
Sumario:The checkpoint with forkhead-associated (FHA) domain and RING-finger (CHFR) protein was identified as a cell cycle checkpoint protein and E3 ubiquitin ligase. In the present study, the potential functions of CHFR in pancreatic cancer were investigated. CHFR expression was measured in five pancreatic cancer cell lines by reverse transcription- quantitative polymerase chain reaction and western blotting. Capan-1 cells stably expressing CHFR were established by lentiviral vector transfection. Cell proliferation was assessed using Cell Counting Kit-8, and cell migration/invasion assay was determined using Transwell assays. Cell cycle and apoptosis induced by gemcitabine or docetaxel were evaluated using flow cytometry. CHFR expression levels were also evaluated in pancreatic ductal adenocarcinoma (PDAC) tumor samples as well as adjacent non-tumor tissues by immunohistochemistry. The significance of CHFR expression was determined, with respect to clinicopathological features and overall survival. Overexpression of CHFR in Capan-1 cells led to a decreased proliferative rate and reduced cell migration and invasion abilities. Results also indicated an increase in G1 phase cells in Capan-1 cells overexpressing CHFR. Docetaxel-induced apoptosis was inhibited in Capan-1 cells with CHFR-overexpression. A reduction in CHFR expression was detected in 51.9% of patients with PDAC, which significantly correlated with later T-stage. The results show CHFR functions as a tumor suppressor in pancreatic cancer, suggests its potential role in controlling the cell cycle of pancreatic cancer cells; however, CHFR overexpression is not a favorable factor in apoptosis induced by docetaxel.