摘要
目的:探讨丝氨酸蛋白酶抑制剂E2(SERPINE2)对黑色素瘤细胞增殖和侵袭的影响及其机制。方法:通过TCGA数据库分析和临床样本的免疫组织化学染色分析SERPINE2在黑痣、黑色素瘤原发灶和转移灶中的表达情况。敲低黑色素瘤A375细胞中SERPINE2的表达,RT-qPCR和免疫印迹检测SERPINE2 mRNA和蛋白表达,CCK8法检测细胞增殖,Transwell实验检测细胞侵袭,免疫印迹检测E-钙黏蛋白(CDH1)、N-钙黏蛋白(CDH2)、SNAI1、基质金属蛋白酶3(MMP3)和基质金属蛋白酶9(MMP9)蛋白表达。结果:TCGA数据库分析显示SERPINE2在黑色素瘤中的表达高于正常组织,免疫组织化学染色显示SERPINE2在黑色素瘤原发灶和转移灶中高表达,敲低SERPINE2可抑制A375细胞的增殖和侵袭,影响上皮间质转化通路分子的表达,其中CDH1的蛋白表达明显增加,CDH2、SNAI1、MMP3和MMP9的蛋白表达明显减少。结论:SERPINE2能促进黑色素瘤细胞增殖和侵袭,其机制涉及调节上皮间质转化相关分子的表达,靶向SERPINE2可作为抑制黑色素瘤进展的一种有前途的策略。
Objective:To investigate the effect and mechanism of serine protease inhibitor E2(SERPINE2)on the proliferation and invasion of melanoma cells.Methods:The expression of SERPINE2 in nevi,melanoma tumors and metastases was analyzed through TCGA database and immunohistochemical staining of clinical samples.After the knockdown of SERPINE2 expression in melanoma cell A375,SERPINE2 mRNA and protein expression were detected by RT-qPCR and Western blotting.CCK8 assay was used to detect cell proliferation,Transwell assay to detect cell invasion,and Western blotting to measure E-cadherin(CDH1),N-cadherin(CDH2),SNAI1,matrix metalloprotease(MMP)3 and MMP9 protein expression.Results:TCGA database analysis revealed that SERPINE2 expression was higher in melanoma compared with normal tissues.Immunohistochemical staining analysis confirmed that SERPINE2 was highly expressed in primary and metastatic melanoma.Knockdown of SERPINE2 significantly inhibited the proliferation and invasion of A375 cells and affected the expression of EMT pathway molecules.Specifically,the expression of CDH1 was significantly increased,while the expression of CDH2,SNAI1,MMP3 and MMP9 were significantly decreased.Conclusion:SERPINE2 promotes the proliferation and invasion of melanoma cells by regulating the expression of epithelial-mesenchymal transition-related molecules and targeting SERPINE2 and may be a promising strategy for inhibiting melanoma tumor progression.
作者
陈珂欣
汪子愉
吴敏靓
王宇翀
熊俊
薛春雨
Chen Kexin;Wang Ziyu;Wu Minliang;Wang Yuchong;Xiong Jun;Xue Chunyu(Department of Plastic Surgery,the First Affiliated Hospital,Naval Medical University,Shanghai 200433,China;Department of Pathology,Faculty of Medical Imaging,Naval Medical University,Shanghai 200433,China)
出处
《解剖学杂志》
2025年第2期143-148,181,共7页
Chinese Journal of Anatomy
基金
军队重点专科项目。
关键词
丝氨酸蛋白酶抑制剂E2
黑色素瘤
增殖
侵袭
上皮间质转化
serine protease inhibitor E2
melanoma
proliferation
invasion
epithelial-mesenchymal transition