中国肿瘤生物治疗杂志2025,Vol.32Issue(6):594-603,10.DOI:10.3872/j.issn.1007-385x.2025.06.005
连接蛋白4/泛酸酯酶1轴对食管鳞状细胞癌细胞恶性生物学行为的影响及其机制
The effect of nectin-4/vanin-1 regulatory axis on the development of esophageal squamous carcinoma and the preliminary investigation of the mechanism
摘要
Abstract
Objective:To explore the expression of nectin-4 and vanin-1 in esophageal squamous cell carcinoma(ESCC)and its influence on the malignant biological behaviors of ESCC cells,as well as the underlying mechanisms.Methods:Transcriptome sequencing combined with GO and KEGG enrichment analysis was used to identify the downstream target gene(vanin-1)regulated by nectin-4.The mRNA expression of vanin-1 in ESCC tissues was studied using the Timer2.0 database,and the mRNA and protein expression of vanin-1 in normal esophageal epithelial HET-1 and ESCC cells was detected by qPCR and Western blot,identifying ESCC KYSE-410 and KYSE-510 cells with the most significant differential expression.The expression of vanin-1 in KYSE-410 and KYSE-510 cells was knocked down using siRNA.The effects of vanin-1 knockdown on cell proliferation,migration,and invasion were measured using CCK-8 assay,wound healing assay,and Transwell chamber assay.Furthermore,KEGG and GO enrichment analyses were conducted for vanin-1-related signaling pathways.Immunohistochemistry was performed to compare the expression of vanin-1 between ESCC tissues and adjacent non-tumor tissues.Results:Timer2.0 database analysis and qPCR results showed that vanin-1 was highly expressed in both ESCC tissues and cell lines(both P<0.01).WB assay also confirmed high expression of vanin-1 protein in ESCC cells(P<0.01).siRNA successfully knocked down vanin-1 expression in KYSE-410 and KYSE-510 cells.Knockdown of vanin-1 significantly inhibited the proliferation,migration,and invasion capabilities of KYSE-410 and KYSE-510 cells(P<0.05 or P<0.01 or P<0.001 or P<0.000 1).KEGG and GO enrichment analysis suggested that vanin-1 might function through pathways related to pantothenic acid and coenzyme A synthesis metabolism.Immunohistochemistry results indicated that vanin-1 was highly expressed in ESCC tissues(P<0.000 1).Conclusion:Vanin-1 is highly expressed in ESCC tissues and promotes the proliferation,migration,and invasion of KYSE-410 and KYSE-510 cells through the nectin-4/vanin-1 axis.Targeting vanin-1 might offer a new therapeutic strategy for ESCC.关键词
食管鳞状细胞癌/连接蛋白4/泛酸酯酶1/迁移/侵袭/增殖Key words
esophageal squamous cell carcinoma(ESCC)/nectin-4/vanin-1/migration/invasion/proliferation分类
医药卫生引用本文复制引用
龙元凤,邓钰滨,杨航,张若兰,杨蜜,宋桂芹,刘康..连接蛋白4/泛酸酯酶1轴对食管鳞状细胞癌细胞恶性生物学行为的影响及其机制[J].中国肿瘤生物治疗杂志,2025,32(6):594-603,10.基金项目
国家自然科学基金(No.82203851) (No.82203851)
四川省自然科学基金(No.023NSFSC0731) (No.023NSFSC0731)
南充市市校合作项目(No.22SXQT0336,No.20SXQT0328) (No.22SXQT0336,No.20SXQT0328)
南充市基础研究平台项目(No.23JCYJPT0027) (No.23JCYJPT0027)
四川省科技厅苗子工程(No.MZGC20240072,No.MZGC20240071) (No.MZGC20240072,No.MZGC20240071)