ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2023; 19(8):2443-2457. doi:10.7150/ijbs.82692 This issue Cite
Research Paper
Decreased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma
1. Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
2. Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
Abstract
Background: Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor of the head and neck, the exact mechanism of which has not been explored.
Methods: By analyzing the GEO data, we found the highly methylated and low expression gene ZNF671. The expression level of ZNF671 in clinical samples was verified by RT-PCR, western blotting and methylation-specific PCR. The function of ZNF671 in LSCC was detected by cell culture and transfection, MTT, Edu, TUNEL assays and flow cytometry analysis. The binding sites of ZNF671 to MAPK6 promoter region were detected and verified by luciferase reporter gene and chromatin immunoprecipitation. Finally, the effect of ZNF671 on LSCC tumors was tested in vivo.
Results: In this study, by analyzing GEO data GSE178218 and GSE59102, we found that zinc finger protein (ZNF671) expression was decreased, and DNA methylation level was increased in laryngeal cancer. Moreover, the abnormal expression of ZNF671 was associated with poor survival prognosis of patients. In addition, we found that overexpression of ZNF671 could inhibit the viability, proliferation, migration and invasion of LSCC cells, while promoting cell apoptosis. In contrast, the opposite effects were observed after knockdown of ZNF671. Through the prediction website and chromatin immunoprecipitation and luciferase reporter experiments, it was found that ZNF671 could bind to the promoter region of MAPK6, thereby inhibiting the expression of MPAK6. In vivo experiments confirmed that overexpression of ZNF671 could inhibit tumor growth.
Conclusion: Our study found that ZNF671 expression was down-regulated in LSCC. ZNF671 up-regulates the expression of MAPK6 by binding to its promoter region, thus participating in cell proliferation, migration and invasion in LSCC. Our study may provide new ideas for early prediction and treatment of LSCC.
Keywords: Laryngeal carcinoma, ZNF671, MAPK6, methylation, proliferation
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