沉默MRPS18A对胆管癌细胞增殖、凋亡、迁移、侵袭的影响及机制  

Effect and Mechanism of Silencing MRPS18A on Proliferation,Apoptosis,Migration and Invasion of Cholangiocarcinoma Cells

作　　者：刘鑫慧 胡守奎 葛洁洁 吕朋举 LIU Xinhui;HU Shoukui;GE Jiejie;L Pengju(Department of Clinical Laboratory,Zhengzhou Central Hospital,Zhengzhou 450007,China)

机构地区：[1]郑州市中心医院检验科,河南郑州450007

出　　处：《河南医学研究》2025年第8期1391-1398,共8页Henan Medical Research

摘　　要：目的 探讨沉默线粒体核糖体蛋白S18a(MRPS18A)对胆管癌细胞增殖、凋亡、迁移、侵袭的影响及相关机制。方法 通过GEPIA2数据库分析MRPS18A在胆管癌组织和正常胆管组织中的相对表达差异,并分析MRPS18A高表达患者与低表达患者的生存期差异。检测MRPS18A在胆管癌细胞和正常胆管上皮细胞中的表达水平。通过细胞转染沉默胆管癌细胞RBE、QBC939中MRPS18A的表达。将RBE、QBC939细胞随机分为si-NC组、si-MRPS18A-1组。MTT和克隆形成实验检测RBE、QBC939细胞增殖水平。流式细胞术和原位末端标记(TUNEL)染色检测RBE、QBC939细胞凋亡水平。Transwell检测RBE、QBC939细胞迁移、侵袭水平。蛋白质免疫印迹(Western blot)检测MRPS18A、p21、Cyclin B1、B细胞淋巴瘤-2相关X蛋白(Bax)、B细胞淋巴瘤-2(Bcl-2)、切割型半胱氨酸天冬氨酸蛋白酶-3(cleaved Caspase-3)、E-钙黏蛋白(E-cad)、N-钙黏蛋白(N-cad)表达水平。结果 MRPS18A在胆管癌组织中表达水平高于正常胆管组织(P<0.05)。MRPS18A高表达胆管癌患者的总生存期和无病生存期低于MRPS18A低表达胆管癌患者(P<0.05)。MRPS18A在胆管癌细胞RBE、QBC939、HuH28、KMBC中的表达水平高于正常胆管上皮细胞HIBEC(P<0.05)。与si-NC组RBE、QBC939细胞比较,si-MRPS18A-1组RBE、QBC939细胞MRPS18A、OD _(450)、克隆形成数、细胞迁移数、细胞侵袭数、Cyclin B1、Bcl-2、N-cad水平降低(P<0.05),凋亡率、凋亡指数、p21、Bax、cleaved Caspase-3、E-cad水平升高(P<0.05)。结论 沉默MRPS18A可抑制胆管癌细胞增殖、迁移、侵袭并诱导细胞凋亡。其机制可能与MRPS18A调控细胞周期、线粒体凋亡通路和上皮间质转化进程有关。Objective To investigate the effect of silencing mitochondrial ribosomal protein S18a(MRPS18A)on proliferation,apoptosis,migration and invasion of cholangiocarcinoma cells and the related mechanism.Methods The relative expression difference of MRPS18A in cholangiocarcinoma tissues and normal bile duct tissues was analyzed by GEPIA2 database,and the survival difference between patients with high expression of MRPS18A and patients with low expression of MRPS18A was analyzed.The expression of MRPS18A in bile duct cancer cells and normal bile duct epithelial cells was detected.The expression of MRPS18A in cholangiocarcinoma cells RBE and QBC939 was silenced by cell transfection.RBE and QBC939 cells were randomly divided into si-NC group and si-MRPS18A-1 group.The proliferation levels of RBE and QBC939 cells were detected by MTT and clonal formation assay.The apoptotic levels of RBE and QBC939 cells were detected by flow cytometry and TdT-mediated dUTP nick and labeling(TUNEL)staining.The migration and invasion levels of RBE and QBC939 cells were detected by Transwell.MRPS18A,p21,Cyclin B1,B-cell lymphoma-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2),cleaved cysteine aspartate protease-3(cleaved Caspase-3),E-cadherin(E-cad)and N-cadherin(N-cad)were detected by Western blot.Results The expression level of MRPS18A in cholangiocarcinoma tissues was higher than that in normal bile duct tissues(P<0.05).The overall survival and disease-free survival of patients with high expression of MRPS18A were lower than those with low expression of MRPS18A(P<0.05).The expression levels of MRPS18A in RBE,QBC939,HuH28 and KMBC in biliary cholangiocarcinoma cells were higher than those in normal biliary duct epithelial cells(P<0.05).Compared with si-NC group,The levels of MRPS18A,OD _(450),clonogenesis number,cell migration number,cell invasion number,Cyclin B1,Bcl-2 and N-cad levels of RBE and QBC939 cells in si-MRPS18A-1 group were decreased(P<0.05).While the apoptosis rate,apoptosis index,p21,Bax,cleaved Caspase-3 and E-cad leve

关 键 词：胆管癌 MRPS18A 增殖 凋亡 迁移 侵袭 

分 类 号：R735[医药卫生—肿瘤]