SETD7通过PI3K-AKT信号通路调节胰腺癌细胞的增殖和迁移  

SETD7 regulates the proliferation and migration of pancreatic cancer cells via the PI3K/AKT signaling pathway

作　　者：高丝 李青[2] 高丽丽 GAO Si;LI Qing;GAO Lili(Department of Biliary-Pancreatic Surgery,Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200127,China;Department of Pathology,Shanghai Pudong New Area People’s Hospital,Shanghai 201299,China;Department of Pathology,Xinhua Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属仁济医院胆胰外科,上海200127 [2]上海市浦东新区人民医院病理科,上海201299 [3]上海交通大学医学院附属新华医院病理科,上海200092

出　　处：《临床与实验病理学杂志》2024年第12期1287-1292,1299,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：浦东新区科技发展基金(PKJ2020-Y40);上海市卫健委卫生行业临床研究专项项目(202140099)。

摘　　要：目的探讨SETD7在胰腺癌发生发展中的作用及其潜在机制。方法利用GEPIA在线数据库分析SETD7在胰腺癌样本中的表达。应用Kaplan-Meier Plotter数据库分析SETD7表达对胰腺癌患者总生存期(overall survival,OS)和无复发生存期(relapse-free survival,RFS)的影响。通过CCK-8、克隆形成、Transwell和划痕愈合实验评估胰腺癌细胞的增殖和迁移能力。采用Western blot法检测SETD7对PI3K/AKT通路的调控作用。结果GEPIA数据库分析发现,SETD7在胰腺癌中表达上调(P<0.05),Kaplan-Meier Plotter数据库分析显示,SETD7高表达组OS和RFS均显著低于低表达组(P<0.001)。在21对匹配的胰腺肿瘤和邻近非肿瘤组织中,肿瘤组织中的SETD7蛋白和mRNA表达明显高于正常组织(P<0.01)。SETD7表达上调可促进胰腺癌细胞增殖和迁移(P<0.01或P<0.05)。SETD7表达下调可导致胰腺癌细胞增殖和迁移能力下降(P<0.01或P<0.05)。SETD7敲减后,p-PI3K和p-AKT的表达减少,SETD7过表达在蛋白水平上均导致p-PI3K和p-AKT表达增加。此外,抑制SETD7,上皮标志物E-cadherin的表达上调,而间充质标志物N-cadherin和vimentin的表达下调,在SETD7过表达细胞中,E-cadherin表达显著下调,而N-cadherin和vimentin的表达显著上调。SETD7可以促进胰腺癌细胞的上皮-间质转化(epithelial-mesenchymal transition,EMT)。结论SETD7通过激活PI3K/AKT信号通路,促进胰腺癌细胞增殖、迁移以及调控EMT。SETD7可能作为胰腺癌的潜在治疗靶点。Purpose This study aims to explore the role of SETD7 in the occurrence and progression of pancreatic cancer and its underlying mechanisms.Methods The expression of SETD7 in pancreatic cancer samples was studied using the Gene Expression Profiling Interactive Analysis(GEPIA)online database.The Kaplan-Meier Plotter database was used to analyze the impact of SETD7 expression on overall survival(OS)and relapse-free survival(RFS)in pancreatic cancer patients.The proliferation and migration abilities of pancreatic cancer cells were evaluated using the CCK-8 colony formation,Transwell,and scratch healing assays.Western blot was used to investigate the regulatory effects of SETD7 on the PI3K/AKT pathway.Results By analyzing GEPIA database,we found that SETD7 was upregulated in pancreatic cancer(P<0.05),the Kaplan-Meier Plotter database analysis showed that OS and DFS were both significantly higher in the low SETD7 expression group than those in the high SETD7 expression(P<0.001).We found that the expression of SETD7 in PC was higher compared with their adjacent non-tumorous tissues(P<0.01).Upregulation of SETD7 promoted the proliferation and migration of pancreatic cancer cells(P<0.01 or P<0.05),while downregulation of SETD7 led to decreased proliferation and migration abilities(P<0.01 or P<0.05).We also found that SETD7 knockdown-induced reduction of p-PI3K and p-AKT.Overexpression of SETD7 resulted in increased expression of p-PI3K and p-AKT.Additionally,SETD7-KD significantly upregulated the expression of the epithelial marker E-cadherin and inhibited the expression of the mesenchymal marker,N-cadherin and vimentin.When SETD7 was increased,the expression levels of E-cadherin were decreased,and the protein expression levels of N-cadherin and vimentin were increased.SETD7 could regulate the PI3K/AKT signaling pathway and promote the epithelial-mesenchymal transition(EMT)of pancreatic cancer cells.Conclusion SETD7 promotes the proliferation and migration of pancreatic cancer cells and regulates EMT by activating the PI3K

关 键 词：胰腺癌 SETD7 PI3K/AKT 增殖 迁移 

分 类 号：R735.9[医药卫生—肿瘤]