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ZNF488 is an independent prognostic indicator in nasopharyngeal carcinoma and promotes cell adhesion and proliferation via collagen IV/FAK/AKT/Cyclin D1 pathway

Authors Zong D, Jiang N, Xu JH, Wang DJ, Zhu HF, Wu LR, Chen C, Yin L, He X

Received 1 January 2019

Accepted for publication 17 May 2019

Published 28 June 2019 Volume 2019:11 Pages 5871—5882

DOI https://doi.org/10.2147/CMAR.S200001

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Xueqiong Zhu


Dan Zong, Ning Jiang, Jian-Hua Xu, De-Jun Wang, Huan-Feng Zhu, Li-Rong Wu, Cheng Chen, Li Yin, Xia He

Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210009, People’s Republic of China

Background: ZNF488 acts as an oncogene which promotes cell invasion and endows tumor cells stem cell capacity in nasopharyngeal carcinoma (NPC), but its correlation with clinicopathologic characteristics and patients’ survival in NPC remain undefined.
Methods: In this study, 158 cases of confirmed NPC were subjected to immunohistochemistry staining for evaluating endogenous expression. Kaplan–Meier method and log-rank test were used to estimate the survival rates. The relationship between ZNF488 and clinicopathological characteristics was statistically calculated by chi-squared test, univariate and multivariate analysis. In addition, adhesion assay, MTT and colony formation assays were performed for measuring adhesion and proliferation capacity. Cell cycle analysis via flow cytometry was conducted to explore cell cycle distribution. Western blot was used to detect pathway protein levels, and the pFAK (Y397) kit was used for focal adhesion kinase (FAK) activation.
Results: We demonstrated that high expression of ZNF488 was significantly correlated with locoregional failure (P=0.018) and distant metastasis (P=0.001). Patients with high ZNF488 expression had poorer overall survival (P<0.001), loco-regional recurrence-free survival (P<0.001), distance metastasis-free survival (P<0.001) and progression-free survival (P<0.001) than those with low ZNF488 group. Multivariate analysis showed that ZNF488 expression was an independent prognostic indicator for predicting NPC patients’ survival (HR, 3.314; 95% CI, 1.489–7.386; P=0.003). Additionally, ZNF488-induced collagen IV/FAK/AKT to enhance adhesion ability meanwhile led to the upregulation of Cyclin D1 to facilitate cell proliferation through promoting cell cycle progression and inhibition of apoptosis through caspase-independent way.
Conclusion: These results reveal that ZNF488, as an independent prognostic indicator, promotes cell adhesion and proliferation through collagen IV/FAK/AKT/Cyclin D1 pathway in NPC.

Keywords: nasopharyngeal carcinoma, ZNF488, proliferation, FAK/AKT/Cyclin D1, prognostic biomarker


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