ADAM15在肝内胆管癌的临床意义及可能作用机制  

Clinical significance and potential mechanism of ADAM15 in intrahepatic cholangiocarcinoma

作　　者：萧展毅 柯逸凡 邹龙 哈睿南 张鹏[1] 邬杰忠 苏惠卿 刘波[1] 胡昆鹏[1] XIAO Zhanyi;KE Yifan;ZOU Long;HA Ruinan;ZHANG Peng;WU Jiezhong;SU Huiqing;LIU Bo;HU Kunpeng(Department of General Surgery,Lingnan Hospital,the Third Afiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510530,China;Department of Obstetrics,the First People's Hospital of Foshan,Foshan,Guangdong 528000,China)

机构地区：[1]中山大学附属第三医院岭南医院普通外科,广东广州510530 [2]佛山市第一人民医院产科,广东佛山528000

出　　处：《热带医学杂志》2023年第4期441-446,I0001,共7页Journal of Tropical Medicine

基　　金：广东省自然科学基金(2021A15150124);东莞市滨海湾中心医院科研项目(2021001)。

摘　　要：目的探讨去整合素-金属蛋白酶15(ADAM15)在肝内胆管癌(ICC)中的表达及其对ICC细胞增殖和迁移能力的影响。方法将加入si-NC-RNA的ICC细胞为对照组、加入si-ADAM15-RNA的ICC细胞为实验组。使用PanCanSurvPlot和Kaplan-Meier plotter分别分析ADAM15在ICC中的表达和其与ICC预后的关系。使用基因富集分析(GSEA)对癌症基因组图谱(TCGA)CHOL数据库中与ADAM15相关的差异表达基因进行KEGG分析。RT-qPCR检测ICC细胞中ADAM15 mRNA的表达。采用siRNA技术沉默ICC细胞中的ADAM15基因,CCK-8实验检测ICC细胞的增殖能力,划痕实验和Transwell实验检测ICC细胞的迁移能力。通过免疫印迹试验探究ADAM15敲低后对细胞周期和迁移相关蛋白的影响。流式细胞术分析ADAM15敲低后对细胞周期的影响。结果ADAM15在ICC组织及ICC细胞中均呈高表达(t>13.14,P<0.05)。ADAM15高表达ICC患者预后较ADAM15低表达患者差,差异有统计学意义(P=5.14e-02,P<0.01)。与si-NC组比较,沉默ADAM15能显著抑制ICC细胞的增殖和迁移能力,差异均有统计学意义(P均<0.05)。与si-NC组相比,沉默ADAM15能明显抑制ICC细胞中的上皮间质转化和细胞周期相关蛋白的表达,差异均有统计学意义(P均<0.05)。结论ADAM15在ICC中高表达,且与ICC患者不良预后相关。沉默ADAM15可抑制ICC细胞增殖、迁移以及EMT通路活性。Objective To explore the expression of desintegrin-metalloproteinase 15(ADAM15)in intrahepatic cholangiocarcinoma(ICC)and its effect on the proliferation and migration of ICC cells.Methods ICC cells with si-NCRNA were used as control and ICC cells with si-ADAM15-RNA as experimental group.ADAM15 expression in ICC and its association with ICC prognosis were analyzed by PanCanSurvPlot and Kaplan-Meier plotter.KEGG analysis of differentexpressed genes associated with ADAM15 in the Cancer Genome Atlas(TCGA)CHOL database was performed using Gene Set Enrichment Analysis(GSEA).ADAM15 m RNA expression in ICC cells was detected by RT-qPCR.ADAM15 gene in ICC cells were knocked down by siRNA technology;the proliferation ability of ICC cells was detected by CCK-8 assay,and the migration ability of ICC cells was detected by scratch assay and transwell assay.The effects of ADAM15 knockdown on cell cycle and migration-related proteins were investigated by western blot assay.Results ADAM15 was highly expressed in ICC tissues and ICC cells(t>13.14,P<0.05),and the prognosis of ICC patients with high ADAM15 expression was worse than those with low ADAM15 expression(P=5.14e-02,P<0.01).ADAM15 knockdown in ICC cells significantly inhibited the proliferation and migration of ICC cells(all P<0.05).ADAM15 silencing could significantly inhibit the expression of epithelial-mesenchymal transition and cell cycle related proteins in ICC cells.Conclusions ADAM15 was overexpressed in ICC and was associated with poor prognosis in ICC patients.ADAM15 knockdown inhibited ICC cell proliferation,migration and EMT pathway activity.

关 键 词：肝内胆管癌 ADAM15 细胞周期 增殖 迁移 

分 类 号：R735.8[医药卫生—肿瘤]