鞘氨醇激酶-1在肺腺癌中的表达及其对A549细胞系上皮间质转化的影响  

Expression of SPHK1 in lung adenocarcinoma and its effect on epithelial mesenchymal transition in A549 cell line

作　　者：严东星 袁晓梅[1] 王金会 YAN Dong-xing;YUAN Xiao-mei;WANG Jin-hui(First Ward,Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453000,Henan,China;不详)

机构地区：[1]新乡医学院第一附属医院呼吸与危重症医学科一病区,河南新乡453000 [2]新乡医学院第一附属医院中西医结合科一病区,河南新乡453000

出　　处：《广东医学》2025年第3期392-398,共7页Guangdong Medical Journal

基　　金：河南省中医药传承与创新人才工程(210999904)。

摘　　要：目的探讨鞘氨醇激酶-1(SPHK1)在肺腺癌中的表达及其对A549细胞增殖、迁移、侵袭及上皮间质转化的影响。方法UALCAN数据库中下载肺腺癌的转录组学数据,其中主要包括515例肺腺癌组织和59例正常肺组织。分析肺腺癌中SPHK1的表达水平及其与患者生存率的关系。利用Western blot和qPCR法检测肺腺癌细胞(H322和A549)及正常肺脏上皮细胞BEAS-2B中SPHK1蛋白及mRNA表达水平的差异。肺腺癌A549细胞根据SPHK1是否敲低,分为si-SPHK1组和si-NC对照组,未作任何处理的细胞为空白对照组。通过CCK-8、划痕实验及Transwell实验分析A549细胞增殖、迁移和侵袭能力的变化。上皮间质转化标志物蛋白[钙黏蛋白E(E-cadherin)、钙黏蛋白N(N-cadherin)和波形蛋白(vimentin)]及mRNA水平采用Western blot和qPCR法检测。结果肺腺癌和正常组织中SPHK1 mRNA表达水平分别为8.467(4.626,15.719)和5.998(3.948,7.926),与正常组织相比,SPHK1 mRNA表达水平在肺腺癌组织中显著升高(P<0.001)。肺腺癌SPHK1 mRNA高表达和低表达患者中位生存时间分别为69个月和108个月,与肺腺癌SPHK1 mRNA低表达组相比,肺腺癌SPHK1 mRNA高表达组生存率显著降低(HR=1.5,P<0.001)。与BEAS-2B细胞相比,肺腺癌H322和A549细胞中SPHK1蛋白及mRNA表达水平显著升高(P<0.05)。SPHK1敲低后能显著抑制肺腺癌A549细胞增殖、迁移和侵袭能力。与空白对照组和si-NC组相比,si-SPHK1组中E-cadherin蛋白及mRNA水平显著升高,而N-cadherin和vimentin蛋白及mRNA表达水平显著降低。结论SPHK1在肺腺癌中显著高表达,SPHK1可能通过上皮间质转化(EMT)过程促进肺腺癌的增殖、迁移和侵袭。SPHK1可能作为治疗肺腺癌的一个潜在靶点。Objective To investigate the expression of SPHK1 in lung adenocarcinoma and its effects on A549 cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT).Methods Transcriptional data from 515 lung adenocarcinoma samples and 59 normal lung tissues were downloaded from the UALCAN database to analyze SPHK1 expression levels and their correlation with patient survival rates.Western blot and qPCR were used to measure SPHK1 protein and mRNA expression in lung adenocarcinoma cell lines(H322 and A549)and normal bronchial epithelial cells(BEAS-2B).A549 cells were divided into si-SPHK1 knockdown group,si-NC control group,and blank control group.CCK-8,scratch,and Transwell assays were employed to assess changes in proliferation,migration,and invasion.EMT markers(E-cadherin,N-cadherin,and vimentin)were evaluated via Western blot and qPCR.Results SPHK1 mRNA levels in adenocarcinoma tissues were significantly higher than in normal tissues[8.467(4.626,15.719)vs.5.998(3.948,7.926),P<0.001].Patients with high SPHK1 expression had a median survival time of 69 months,compared to 108 months for those with low expression(HR=1.5,P<0.001).SPHK1 protein and mRNA levels were also significantly elevated in H322 and A549 cells compared to BEAS-2B(P<0.05).Knockdown of SPHK1 significantly inhibited A549 cell proliferation,migration,and invasion.E-cadherin levels increased significantly in the si-SPHK1 group,while N-cadherin and vimentin levels decreased compared to controls.Conclusion SPHK1 is significantly overexpressed in lung adenocarcinoma and may promote cell proliferation,migration,and invasion through EMT processes.SPHK1 could serve as a potential therapeutic target for lung adenocarcinoma.

关 键 词：肺腺癌 鞘氨醇激酶-1 预后 上皮间质转化 

分 类 号：R73-37[医药卫生—肿瘤] R734.2[医药卫生—临床医学]