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

Zhang,Di; Xu,Xiao‑Lan; Li,Fei; Sun,Hai‑Chen; Cui,Ye‑Qing; Liu,Shuang; Xu,Ping‑Yong

doi:10.3892/ol.2017.7239

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

Authors:
- Di Zhang
- Xiao‑Lan Xu
- Fei Li
- Hai‑Chen Sun
- Ye‑Qing Cui
- Shuang Liu
- Ping‑Yong Xu
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Affiliations: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China, National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/ol.2017.7239
Pages: 8042-8050
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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