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ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/β-Catenin Pathway

Authors Zhan W, Li Y, Liu X, Zheng C, Fu Y

Received 24 October 2019

Accepted for publication 31 December 2019

Published 24 January 2020 Volume 2020:12 Pages 599—610

DOI https://doi.org/10.2147/CMAR.S235933

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Chien-Feng Li


Wei Zhan, 1 Yuzhe Li, 2 Xuhui Liu, 1 Changlong Zheng, 1 Yongmei Fu 1

1Department of Emergency, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, People’s Republic of China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Sun Yat-Sen University, Lingnan Hospital, Guangzhou 510080, People’s Republic of China

Correspondence: Yongmei Fu
Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, People’s Republic of China
Email fuyongmei2019@126.com
Changlong Zheng
The Third Hospital of Sun Yat-Sen University, Guangzhou 510630, China
Email zhengchanglong@163.com

Background: Lung cancer is the most common cancer in the world and is the main cause of cancer-related death. Revealing the potential mechanism of malignant characteristics of lung cancer is urgent for treating this disease effectively. Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. The role of ZNF671 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of this study was to investigate the function and mechanism of ZNF671 in NSCLC.
Methods: ZNF671 expression in NSCLC cells and tissues were detected by Real-Time PCR, Western blot and TCGA databases. Then, we evaluated the prognostic value of ZNF671 expression in NSCLC using the Kaplan–Meier plotter (KM plotter) and TCGA databases. Moreover, the function of ZNF671 in the proliferation and metastasis of lung cancer was investigated by MTT assay, colony formation assay, in vivo experiment, EdU assay, wound healing assay, transwell assay, and 3D culture assay. Luciferase reporter and subcellular fractionation assays were performed to determine the underlying mechanism of ZNF671-mediated proliferation and metastasis of NSCLC.
Results: ZNF671 expression was significantly reduced in both NSCLC cell lines and clinical specimens compared to that in normal controls. The survival analysis results indicated that the downregulation of ZNF671 significantly correlates with poor prognosis and predicts a shorter overall survival and post-progression survival among NSCLC patients. Ectopic overexpression of ZNF671 dramatically restrains, whereas silencing ZNF671 enhanced, cell proliferation and metastasis of NSCLC. Mechanically, gene set enrichment analysis (GSEA) showed that the expression of ZNF671 was significantly correlated with Wnt/β-catenin signaling. Simultaneously, our results confirm that the overexpression of ZNF671 inhibits cell cycle progression and metastasis by weakening the Wnt/β-catenin pathway, and then downregulating the expression of downstream target genes CyclinD1 and MMP9.
Conclusion: This study found that the overexpression of ZNF671 restrains the proliferation and metastasis of lung cancer through inhibiting Wnt/β-catenin signaling pathway. Furthermore, our current results provide important insights into ZNF671 as an excellent predictive biomarker for NSCLC, thus providing a novel perspective for the treatment of NSCLC.

Keywords: zinc finger protein 671, proliferation, metastasis, Wnt/β-catenin pathway, biomarker

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