PMID- 37215982 OWN - NLM STAT- MEDLINE DCOM- 20230530 LR - 20230710 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 19 IP - 8 DP - 2023 TI - Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma. PG - 2443-2457 LID - 10.7150/ijbs.82692 [doi] AB - 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. CI - (c) The author(s). FAU - Zhang, Wei AU - Zhang W AD - Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Liu, Ting AU - Liu T AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Li, Xinyi AU - Li X AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Li, Tianshu AU - Li T AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Ma, Xiangchi AU - Ma X AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Zhao, Dongxu AU - Zhao D AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. FAU - Zhao, Xudong AU - Zhao X AD - Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230508 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 0 (MicroRNAs) RN - 0 (Tumor Suppressor Proteins) RN - 0 (ZNF671 protein, human) SB - IM MH - Humans MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - DNA Methylation/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - *Laryngeal Neoplasms/genetics/pathology MH - *MicroRNAs/metabolism MH - *Squamous Cell Carcinoma of Head and Neck/genetics/pathology MH - *Tumor Suppressor Proteins/genetics PMC - PMC10197888 OTO - NOTNLM OT - Laryngeal carcinoma OT - MAPK6 OT - ZNF671 OT - methylation OT - proliferation COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2023/05/22 19:11 MHDA- 2023/05/24 06:42 PMCR- 2023/01/01 CRDT- 2023/05/22 12:32 PHST- 2023/01/16 00:00 [received] PHST- 2023/04/15 00:00 [accepted] PHST- 2023/05/24 06:42 [medline] PHST- 2023/05/22 19:11 [pubmed] PHST- 2023/05/22 12:32 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - ijbsv19p2443 [pii] AID - 10.7150/ijbs.82692 [doi] PST - epublish SO - Int J Biol Sci. 2023 May 8;19(8):2443-2457. doi: 10.7150/ijbs.82692. eCollection 2023.