[摘 要] 目的：探究连接蛋白4/泛酸酯酶1轴在食管鳞状细胞癌（ESCC）中的表达和其对ESCC细胞恶性生物学行为的影响 及机制。方法：转录组测序结合GO和KEGG富集分析筛选出连接蛋白4调控下游靶基因泛酸酯酶1，用数据库Timer2.0分析泛 酸酯酶1 mRNA在ESCC组织中的表达，并用qPCR和WB法检测正常食管上皮细胞HET-1和ESCC细胞中泛酸酯酶1 mRNA和 蛋白的表达，筛选出表达差异最为显著的ESCC KYSE-410和KYSE-510细胞。用siRNA敲减KYSE-410和KYSE-510细胞中泛 酸酯酶1的表达，用CCK-8法、划痕愈合实验和Transwell小室实验检测敲减泛酸酯酶1表达对细胞增殖、迁移和侵袭的影响。此 外，对泛酸酯酶1相关信号通路进行KEGG和GO富集分析，并采用免疫组化法比较泛酸酯酶1在ESCC组织和癌旁组织中的表 达差异。结果：Timer2.0数据库数据分析和qPCR法检测结果显示，泛酸酯酶1在ESCC组织和细胞中呈高表达（均P < 0.01）。 WB法检测结果显示，泛酸酯酶1蛋白在ESCC细胞中高表达（P < 0.01）。siRNA成功敲减了KYSE-410和KYSE-510细胞中泛酸 酯酶1的表达。敲减泛酸酯酶1能显著抑制KYSE-410和KYSE-510细胞的增殖、迁移和侵袭能力（P < 0.05或P < 0.0 1或P < 0.00 1 或P < 0.000 1）。KEGG和GO富集分析提示泛酸酯酶1可能通过参与泛酸和辅酶A的合成代谢途径发挥作用。免疫组化法检测 结果显示，泛酸酯酶1在ESCC组织中呈高表达（P < 0.000 1）。结论：泛酸酯酶1在ESCC组织中呈高表达，通过连接蛋白4/泛 酸酯酶1轴促进KYSE-410和KYSE-510细胞增殖、迁移和侵袭能力。靶向抑制泛酸酯酶1可能为ESCC的治疗提供新的思路。

[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.

国家自然科学基金（No. 82203851）；四川省自然科学基金（No. 023NSFSC0731）；南充市市校合作项目（No.22SXQT0336， No.20SXQT0328）；南充市基础研究平台项目（No.23JCYJPT0027）；四川省科技厅苗子工程（No.MZGC20240072，No.MZGC20240071）