Role of up-regulated DDX3 in the proliferation of human cervical cancer cells
10.3760/cma.j.cn112151-20200519-00394
- VernacularTitle:DDX3表达上调在人宫颈癌细胞增殖中的作用分析
- Author:
Fangfang GUO
1
;
Ruijiao ZHAO
;
Dujuan LI
;
Ziguang XU
;
Lingfei KONG
Author Information
1. 河南省人民医院病理科，郑州 450000
- Keywords:
Uterine cervical neoplasms;
Cell proliferation;
Neoplasm invasiveness;
DDX3;
PI3K/Akt signaling pathway
- From:
Chinese Journal of Pathology
2021;50(2):119-124
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of DDX3 up-regulation in the proliferation of human cervical cancer cells and its correlation with clinical prognosis.Methods:Expression levels of DDX3 in the 59 specimens of cervical cancer and adjacent non-neoplastic tissue collected at Henan Provincial People′s Hospital from April 2012 to March 2013 were detected using immunohistochemistry. A lentivirus-mediated DDX3-over-expression cell line was constructed based on HeLa cells of cervical cancer. CCK-8 assay was used to evaluate cell survival rate. Boyden chamber was used to measure the cell migration and invasion. Real-time fluorescence quantitative PCR was used to detect DDX3 expression level and Western blot was used to detect the expression of EMT and PI3K/Akt signal pathway-related proteins. Results:DDX3 overexpression was associated with FIGO stage, depth of cervical invasion and lymph node metastasis ( P<0.05). Kaplan-Meier analysis revealed that cervical cancer patients with high expression of DDX3 had a poor overall survival ( P<0.05). Compared with the cells transfected with pLVX-Con vector, the expression of DDX3 protein and mRNA was significantly increased in the cells transfected with pLVX-DDX3 (all P<0.01). Cell proliferation was significantly increased following transfection with pLVX-DDX3 for 72 h in HeLa cells compared with that transfected with pLVX-Con ( P<0.05). Compared with the controls, DDX3 overexpression significantly promoted the migration and invasion of HeLa cells ( P<0.05), and increased the expression of N-Cadherin, vimentin and Snail in HeLa cells ( P<0.05). In pLVX-DDX3 group, the expression levels of β-catenin, phosphorylated Akt, and pAkt′s downstream target p-GSK3β were significantly higher than those of pLVX-Con group ( P<0.05). The expression levels of p-Akt, p-GSK3β and β-catenin were decreased when the PI3K/Akt pathway was blocked using the PI3K inhibitor LY294002 ( P<0.05), and the expression levels of N-Cadherin, vimentin and Snail were also significantly decreased ( P<0.05). Conclusions:DDX3 overexpression promotes proliferation, migration and invasion of cervical cancer cells, and induces epithelial-mesenchymal transition (EMT). Its mechanism may be related to activation of the PI3K/Akt signaling pathway.
