LncRNA TUG1靶向AKT/mTOR信号通路促进卵巢癌细胞增殖和转移的研究  

Study on the LncRNA TUG1 Facilitating Ovarian Cancer Cell Proliferation and Metastasis via Targeting the AKT/mTOR Signaling Pathway

作　　者：蔡阳阳[1] 吴向晖[1] 熊丽丽[1] CAI Yangyang;WU Xianghui;XIONG Lili(The First Affiliated Hospital of Henan University of Science and Technology,Luoyang,471000)

机构地区：[1]河南科技大学第一附属医院,471000

出　　处：《实用癌症杂志》2024年第6期883-886,共4页The Practical Journal of Cancer

摘　　要：目的探究长链非编码RNA牛磺酸上调基因1(lncRNA TUG1)通过介导蛋白激酶B/磷酸化哺乳动物雷帕霉素靶蛋白(AKT/mTOR)信号通路对卵巢癌细胞增殖和转移的影响及可能机制。方法收集112例行卵巢癌根治术患者的卵巢癌组织及癌旁组织,采用RT-PCR检测两组织、卵巢癌细胞(OC3,SKOV3,A2780,HO-8910)及人正常卵巢上皮细胞IOSE80中TUG1表达。选择SKOV3细胞并分为si-TUG1组(转染TUG1 shRNA)和NC组(转染空载体质粒),采用CCK8、流式细胞术、划痕实验检测2组细胞增殖水平、细胞周期及细胞转移能力,Western blot检测2组蛋白激酶B(AKT)、磷酸化哺乳动物雷帕霉素靶蛋白(mTOR)、p-AKT、p-mTOR、细胞周期相关蛋白(Cyclin D1,Cyclin B1,CDK6)、转移相关蛋白(MMP-2,Snail)的相对表达量。结果RT-PCR检测结果显示,卵巢癌组织中TUG1表达高于癌旁组织(P<0.05),卵巢癌细胞OC3,SKOV3,A2780,HO-8910中TUG1表达均高于IOSE80细胞,且SKOV3中TUG1表达最高(P<0.05)。si-TUG1组细胞增殖水平、G_(2)/M期比例、细胞迁移距离均低于NC组,细胞G_(0)/G_(1)期比例高于NC组(P<0.05);si-TUG1组p-AKT/AKT、p-mTOR/mTOR、Cyclin D1、Cyclin B1、CDK6、MMP-2,Snail蛋白表达低于NC组(P<0.05)。结论下调lncRNA TUG1表达能降低卵巢癌细胞增殖、转移能力,这可能与其能抑制AKT/mTOR信号通路有关。Objective To explore the effect and the possible mechanism of long noncoding RNA taurine-upregulated gene 1(lncRNA TUG1)on the proliferation and metastasis of ovarian cancer cells by mediating protein kinase B/mammalian target of rapamycin(AKT/mTOR)signaling pathway.Methods The pairs of ovarian cancer tissues and adjacent normal tissues were collected from 112 ovarian cancer patients.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the expression of TUG1 in the selected tissues,ovarian cancer cell lines(OC3,SKOV3,A2780,HO-8910)and human ovarian normal epithelial cell line IOSE80.SKOV3 cells were assigned to either TUG1 shRNA transfection(si-TUG1 group)or empty vector plasmid transfection(NC group),thereafter,the ovarian cancer cell proliferation,cycle and metastasis profiles were detected using CCK8 assay,flow cytometry and scratch test.The relative expression levels of AKT,mTOR,phosphorylated AKT(p-AKT),phosphorylated mTOR(p-mTOR),cell cycle-related proteins(Cyclin D1,Cyclin B1,CDK6),and metastasis-related proteins(MMP-2,Snail)in each group were measured by Western blot.Results RT-PCR denoted that TUG1 expression was higher in ovarian cancer tissues than in adjacent normal tissues(P<0.05).TUG1 expression was higher in ovarian cancer cell lines OC3,SKOV3,A2780,and HO-8910 than in IOSE80 cells,and TUG1 expression was the highest in SKOV3(P<0.05).The cell proliferation,cell cycle arrest at G_(2)/M phase and cell migration distance were all smaller in si-TUG1 group than in NC group,and the cell cycle arrest at G_(0)/G_(1) phase was higher in si-TUG1 group than in NC group(P<0.05).The protein expression of p-AKT/AKT,p-mTOR/mTOR,Cyclin D1,Cyclin B1,CDK6,MMP-2,and Snail in si-TUG1 group was lower than those in NC group(P<0.05).Conclusion Down-regulation of lncRNA TUG1 expression can attenuate the proliferation and metastasis ability of ovarian cancer cells,which may be related to the inhibition of the AKT/mTOR signaling pathway.

关 键 词：长链非编码RNA牛磺酸上调基因1 卵巢癌 增殖 AKT/MTOR 

分 类 号：R737.31[医药卫生—肿瘤]