lncRNA GNG12-AS1在胶质瘤患者组织中的表达及其对脑胶质瘤细胞中PI3K/Akt/mTOR信号通路的影响  

Expression of lncRNA GNG12-AS1 in Glioma Tissues and Its Impact on the PI3K/Akt/mTOR Signaling Pathway in Glioma Cells

作　　者：贾海波[1] 李艳玲[2] 程彬 任洪波[1] JIA Hua-bo;LI Yan-ling;CHENG Bin;REN Hongbo(Department of Neurosurgery,Handan Central Hospital,Handan 056001,China;Department of Geriatrics,Handan First Hospital,Handan 056001,China;Department of Neurosurgery,the Second Affiliated Hospital of Xingtai Medical College,Xingtai 054000,China)

机构地区：[1]邯郸市中心医院神经外三科,邯郸056001 [2]邯郸市第一医院老年病二科,邯郸056001 [3]邢台医学高等专科学校第二附属医院神经外一科,邢台054000

出　　处：《中国临床神经科学》2024年第2期121-129,共9页Chinese Journal of Clinical Neurosciences

基　　金：河北省卫生健康委2023年度医学科学研究课题计划(编号:20231943)。

摘　　要：目的探究长链非编码RNA(lncRNA)GNG12-AS1在胶质瘤组织中的表达及其对PI3K/Akt/mTOR信号通路的影响。方法qRT-PCR法检测胶质瘤组织及不同胶质瘤细胞系中GNG12-AS1的表达,将人神经胶质瘤细胞(U251细胞)依据不同干预方法分为对照组、si-NC组、si-GNG12-AS1组、si-GNG12-AS1+740 Y-P组。转染培养48 h后,利用CCK-8法检测各组细胞的增殖活性;克隆形成实验检测各组细胞增殖;Transwell小室实验检测各组细胞迁移和侵袭能力;划痕愈合实验检测各组细胞的迁移;Western blot法检测各组细胞中PI3K、p-PI3K、Akt、p-Akt、mTOR、p-mTOR蛋白的表达;建立移植瘤裸鼠模型并检测肿瘤生长情况。结果与癌旁组织和正常脑胶质细胞比较,胶质瘤组织和细胞中GNG12-AS1表达水平均增高(均P<0.05);与对照组比较,si-GNG12-AS1组细胞存活率、克隆形成数量、迁移和侵袭细胞数、划痕愈合率以及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR比值均降低(均P<0.05),体内移植瘤组织的重量和体积减小(均P<0.05);与si-GNG12-AS1组比较,si-GNG12-AS1+740 Y-P组细胞存活率、克隆形成数量、迁移和侵袭细胞数、划痕愈合率以及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR比值均升高(均P<0.05),体内移植瘤组织的重量和体积增加(均P<0.05)。结论GNG12-AS1在胶质瘤组织中高表达,敲低GNG12-AS1可通过激活PI3K/Akt/mTOR信号通路抑制胶质瘤的恶性发展。Aim To investigate the expression of long non-coding RNA(lncRNA)GNG12-AS1 in glioma tissues and its impact on the PI3K/Akt/mTOR signaling pathway in glioma cells.Methods qRTPCR was applied to detect the expression of GNG12-AS1 in glioma tissue and different glioma cell lines.Subsequently,human glioma U251 cells were divided into a control group,a si-NC group,a si-GNG12-AS1 group,and a si-GNG12-AS1+740 Y-P group according to different intervention methods.After 48 hours of transfection culture,CCK-8 was applied to detect the proliferative activity of cells in each group.Clone formation experiment was applied to detect cell proliferation in each group.Transwell chamber test was applied to detect cell migration and invasion abilities of each group.Scratch healing experiment was applied to detect the migration of cells in each group.Western blot was applied to detect the expression of PI3K,p-PI3K,Akt,p-Akt,mTOR,and p-mTOR proteins of cells in each group.A nude mouse model of transplanted tumors was established and tumor growth was detected.Results Compared with adjacent cancer tissues and normal brain glial cells,the expression of GNG12-AS1 in glioma tissues and cells increased(P<0.05).Compared with the control group,the survival rate,number of clones formed,numbers of migrating and invading cells,scratch healing rate,and the ratios of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR in the si-GNG12-AS1 group decreased(P<0.05),the weight and volume of transplanted tumor tissue in vivo decreased(P<0.05).Compared with the si-GNG12-AS1 group,the survival rate,number of clones formed,number of migrating and invading cells,scratch healing rate,and the ratios of p-PI3K/PI3K,p-Akt/Akt,and p-mTOR/mTOR in the si-GNG12-AS1+740 Y-P group increased(P<0.05),the weight and volume of transplanted tumor tissue in vivo increased(P<0.05).Conclusion GNG12-AS1 is highly expressed in glioma tissue,and knocking down GNG12-AS1 can inhibit the malignant development of glioma by activating the PI3K/Akt/mTOR signaling pathway.

关 键 词：长链非编码RNA GNG12-AS1 胶质瘤 磷脂酰肌醇-3-激酶 蛋白激酶B 雷帕霉素靶蛋白 

分 类 号：R730.264[医药卫生—肿瘤]