PREX1/RAC1分子轴对人胆管癌细胞恶性生物学特性的影响  

Effect of PREX1/RAC1 axis on the malignant biological behavior of human cholangiocarcinoma cells

作　　者：张国华[1] 周通[1] 张西坤 马艳娜 刘其雨[3] 谭大勇[1] ZHANG Guohua;ZHOU Tong;ZHANG Xikun;MA Yanna;LIU Qiyu;TAN Dayong(Department of Hepatobiliary and Pancreas,Affiliated Hospital of Qinghai University(Tumor Hospital of QinghaiUniversity),Qinghai Xining 810001,China;Department of General Surgery,Qinghai Provincial People'sHospital,Qinghai Xining 810007,China;Department of Hepatobiliary Surgery,Kunming First People's Hospital,YunnanKunming 650031,China)

机构地区：[1]青海大学附属医院(青海大学附属肿瘤医院)肝胆胰一科,青海西宁810001 [2]青海省人民医院普外科,青海西宁810007 [3]昆明市第一人民医院肝胆外科,云南昆明650031

出　　处：《现代肿瘤医学》2022年第11期1925-1931,共7页Journal of Modern Oncology

基　　金：云南省科技计划项目(编号:2017FE468-235);青海大学附属医院中青年科研基金项目(编号:ASRF-2017-YB-08)。

摘　　要：目的:探讨PREX1/RAC1分子轴对人胆管癌细胞恶性生物学特性的影响。方法:Ualcan和GEPIA 1.0数据库预测PREX1、PREX2和RAC1在胆管癌中的表达差异和生存曲线。蛋白质印记(Western blotting)和荧光定量PCR(RT-qPCR)检测PREX1、PREX2、RAC1、E-cadherin、N-cadherin、Vimentin蛋白和mRNA在胆管癌组织和细胞系中的表达水平。CCK-8试剂盒、BrdU试剂盒和克隆形成实验分别检测RBE细胞增殖、BrdU阳性细胞比例和克隆能力。采用划痕和Transwell分别检测RBE细胞迁移和侵袭。免疫荧光染色对E-cadherin和N-cadherin进行定位和定量。结果:Ualcan和GEPIA 1.0数据库预测发现,PREX1和RAC1在包括胆管癌在内的多种恶性肿瘤中异常高表达,且高表达的PREX1和RAC1预示着胆管癌患者有较好的生存率。此外,PREX1和RAC1在胆管癌组织和细胞系中高表达。PREX1能够上调RAC1的表达水平。过表达或敲低PREX1增高或降低RBE细胞增殖、克隆能力、迁移、侵袭和上皮间充质转化。结论:我们首次发现PREX1和RAC1在胆管癌样本中异常高表达,且PREX1/RAC1分子轴促进人胆管癌细胞增殖、迁移、侵袭和上皮间充质转化。Objective:To explore the effect of PREX1/RAC1 axis on the malignant biological behavior of human cholangiocarcinoma cells.Methods:Ualcan and GEPIA 1.0 database predicted the expression difference and survival curve of PREX1,PREX2 and RAC1 in cholangiocarcinoma.Western blotting and RT-qPCR were used to detect expression of PREX1,PREX2,RAC1,E-cadherin,N-cadherin and Vimentin protein and mRNA in cholangiocarcinoma tissues and cell lines.CCK-8,BrdU kit and colony-forming unit assays were used to detect the proliferation,the proportion of BrdU positive cells and cloning ability of RBE cells,respectively.Migration and invasion of RBE cells were detected by wound scratch and Transwell assay,respectively.Immunofluorescence staining was used to locate and quantify E-cadherin and N-cadherin.Results:Ualcan and GEPIA 1.0 database predicted that PREX1 and RAC1 were highly expressed in a variety of malignant tumors including cholangiocarcinoma,and the high expression of PREX1 and RAC1 predicted a better survival rate for patients with cholangiocarcinoma.Moreover,PREX1 and RAC1 were highly expressed in tissues and cell lines of cholangiocarcinoma.PREX1 up-regulated RAC1 expression.Overexpressing or knocking down PREX1 increased or reduced proliferation,clonality,migration,invasion and epithelial-mesenchymal transformation of RBE cells.Conclusion:We firstly found that PREX1 and RAC1 are highly expressed in cholangiocarcinoma samples,and the PREX1/RAC1 axis promotes the proliferation,migration,invasion and epithelial-mesenchymal transformation of human cholangiocarcinoma cells.

关 键 词：人胆管癌 恶性生物学特性 PREX1 RAC1 

分 类 号：R735.8[医药卫生—肿瘤]