ZNF488 Enhances the Invasion and Tumorigenesis in Nasopharyngeal Carcinoma Via the Wnt Signaling Pathway Involving Epithelial Mesenchymal Transition.
- Author:
Dan ZONG
1
;
Li YIN
;
Qian ZHONG
;
Wen Jie GUO
;
Jian Hua XU
;
Ning JIANG
;
Zhi Rui LIN
;
Man Zhi LI
;
Ping HAN
;
Lin XU
;
Xia HE
;
Mu Sheng ZENG
Author Information
- Publication Type:In Vitro ; Original Article
- Keywords: ZNF488; Nasopharyngeal carcinoma; Invasion; Carcinogenesis; Epithelial-mesenchymal transition; Wnt signaling pathway
- MeSH: Blotting, Western; Carcinogenesis*; Cell Line; Clone Cells; Epithelial-Mesenchymal Transition*; Epithelium; Fluorescent Antibody Technique; Gene Expression Profiling; Heterografts; Luciferases; Microarray Analysis; Oncogenes; Polymerase Chain Reaction; Reverse Transcription; RNA, Small Interfering; Wnt Signaling Pathway*; Wound Healing; Zidovudine; Zinc Fingers
- From:Cancer Research and Treatment 2016;48(1):334-344
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The purpose of this study was to investigate the function of Zinc finger protein 488 (ZNF488) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: The endogenous expression of ZNF488 in NPC tissues, normal nasopharyngeal epithelium tissues and NPC cell lines were detected by quantitative reverse transcription polymerase chain reaction. ZNF488 over-expressing and knock-down NPC cell line models were established through retroviral vector pMSCV mediated over-expression and small interfering RNA (siRNA) mediated knock-down. The invasion and migration capacities were evaluated by wound healing and transwell invasion assays in ZNF488 over-expressing and control cell lines. Soft-agar colony formation and a xenograft experiment were performed to study tumorigenic ability in vitro and in vivo. Immunofluorescence and western blotting analysis were used to examine protein changes followed by ZNF488 over-expression. Microarray analysis was performed to explore gene expression profilings, while luciferase reporter assay to evaluate the transcriptive activity of Tcf/Lef. RESULTS: ZNF488 was over-expressed in NPC tissues compared with normal tissues, especially higher in 5-8F and S18, which are well-established high metastatic NPC clones. Functional studies indicate that over-expression of ZNF488 provokes invasion, whereas knock-down of ZNF488 alleviates invasive capability. Moreover, over-expression of ZNF488 promotes NPC tumor growth both in vitro and in vivo. Our data further show that over-expression of ZNF488 induces epithelial mesenchymal transition (EMT) by activating the WNT/beta-catenin signaling pathway. CONCLUSION: Our data strongly suggest that ZNF488 acts as an oncogene, promoting invasion and tumorigenesis by activating the Wnt/beta-catenin pathway to induce EMT in NPC.
