长链非编码RNA PVT1调控表皮生长因子受体/有丝分裂原活性蛋白激酶通路对卵巢癌细胞的影响实验研究  

Effect of long non-coding RNA PVT1 on ovarian cancer cells by regulating epidermal growth factor receptor/mitogen-activated protein kinase pathway

作　　者：王静 张虹宇 张磊 赵仰光 王健[4] WANG Jing;ZHANG Hongyu;ZHANG Lei;ZHAO Yangguang;WANG Jian(Department of Gynecologic Oncology,Tianjin Medical University Cancer Hospital,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院妇瘤科,天津300060 [2]秦皇岛市第四医院妇瘤科,河北秦皇岛066001 [3]秦皇岛市第四医院介入科,河北秦皇岛066001 [4]河北医科大学第三医院妇产科,河北石家庄050051

出　　处：《陕西医学杂志》2024年第11期1454-1458,共5页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81969826);河北省秦皇岛市科学技术研究与发展计划项目(202101A116)。

摘　　要：目的:探讨长链非编码RNA(lncRNA)人浆细胞瘤转化迁移基因1(PVT1)调控表皮生长因子受体(EGFR)/有丝分裂原活性蛋白激酶(MAPK)通路对卵巢癌细胞的影响。方法:将人卵巢癌细胞SKOV-3分为对照组(空白未处理)、si-NC组(转染携带空载体慢病毒)、si-lncRNA PVT1组(转染lncRNA PVT1 siRNA)。另选取人正常卵巢上皮细胞系HOSE为正常组。采用RT-qPCR检测细胞中lncRNA PVT1表达。采用Transwell实验、平板克隆实验分别检测SKOV-3细胞侵袭以及克隆形成能力。采用流式细胞术检测SKOV-3细胞凋亡情况。采用Western blot检测细胞中EGFR、细胞外信号调节蛋白激酶1/2(ERK1/2)、p-ERK1/2蛋白表达。根据细胞分组,将BALB/c裸鼠也相应随机分为对照组、si-NC组、si-lncRNA PVT1组,每组8只。建立裸鼠皮下移植瘤模型。比较各组裸鼠不同时间皮下移植瘤体积及平均瘤体重量。结果:对照组SKOV-3细胞lncRNA PVT1表达水平高于si-lncRNA PVT1组,si-lncRNA PVT1组SKOV-3细胞lncRNA PVT1表达水平高于正常组人卵巢正常上皮细胞系HOSE(均P<0.05)。与对照组及si-NC组比较,si-lncRNA PVT1组SKOV-3细胞克隆形成率、侵袭细胞数、EGFR、p-ERK1/2蛋白表达水平降低,细胞凋亡率升高(均P<0.05)。与对照组及si-NC组比较,si-lncRNA PVT1组裸鼠28 d时皮下移植瘤体积以及平均瘤体重量降低(均P<0.05)。结论:lncRNA PVT1在卵巢癌细胞中高表达,干扰其表达可抑制卵巢癌细胞侵袭、克隆、凋亡以及裸鼠皮下成瘤速度,作用机制可能与调控EGFR/MAPK信号通路有关。Objective:To explore the effect of long non-coding RNA(lncRNA)PVT1 on ovarian cancer cells by regulating epidermal growth factor receptor(EGFR)/mitogen-activated protein kinase(MAPK)pathway.Methods:Human ovarian cancer cells SKOV-3 were divided into control group(blank),si-NC group(transfected with empty carrier lentivirus)and si-lncRNA PVT1 group(transfected with lncRNA PVT1 siRNA).The normal human ovarian epithelial cell line HOSE was selected as the normal group.The expression of lncRNA PVT1 in cells was detected by RT-qPCR.Transwell assay and plate cloning assay were used to detect the invasion and cloning ability of SKOV-3 cells.The apoptosis of SKOV-3 cells was detected by flow cytometry.The expression of EGFR,extracellular signal-regulated protein kinase 1/2(ERK1/2)and p-ERK1/2 proteins were detected by Western blot.According to cell grouping,BALB/c nude mice were randomly divided into control group,si-NC group and si-lncRNA PVT1 group,with 8 mice in each group.The model of subcutaneous tumor transplantation in nude mice was established.The tumor volume and average tumor weight of subcutaneous transplantation were compared in each group.Results:lncRNA PVT1 expression level in SKOV-3 cells of control group was higher than that in si-lncRNA PVT1 group,and lncRNA PVT1 expression level in SKOV-3 cells of si-lncRNA PVT1 group was higher than that in HOSE of human ovarian normal epithelial cell line of normal group(all P<0.05).Compared with the control group and the si-NC group,the clonal formation rate of SKOV-3 cells,the number of invasive cells,the expression levels of EGFR and p-ERK1/2 protein in si-lncRNA PVT1 group were decreased,and the apoptosis rate was increased(all P<0.05).Compared with the control group and the si-NC group,the subcutaneous graft tumor volume and average tumor weight of nude mice in the si-lncRNA PVT1 group at 28 days were decreased(all P<0.05).Conclusion:LncRNA PVT1 is highly expressed in ovarian cancer cells,and interfering with its expression can inhibit the invasion,colony formati

关 键 词：卵巢癌 长链非编码RNA PVT1 表皮生长因子受体/有丝分裂原活性蛋白激酶通路 细胞侵袭 细胞凋亡 移植瘤 

分 类 号：R36[医药卫生—病理学]