长链非编码RNA LINC01235通过调控磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路影响胃癌进展的机制  

Effects of long non-coding RNA LINC01235 on progression of gastric cancer via modulating phosphoinositide-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

作　　者：程华[1] 张卓奇[1] 张牙 李杰[1] 彭鑫宇[1] 问明[1] 郭剑[1] 张爱民[1] Cheng Hua;Zhang Zhuoqi;Zhang Ya;Li Jie;Peng Xinyu;Wen Ming;Guo Jian;Zhang Aimin(Department of Gastrointestinal Surgery,Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院胃肠外科,保定071000

出　　处：《中华实验外科杂志》2021年第8期1503-1506,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨长链非编码RNA LINC01235在胃癌中的表达及其作用机制。方法肿瘤基因组图谱(TCGA)数据库检测LINC01235在胃癌及癌旁组织的表达;分析LINC01235对胃癌患者预后的价值;收集新鲜胃癌及癌旁组织验证生物信息学结果。调控人胃癌细胞株MGC-803、SGC-7901中LINC01235表达,检测细胞增殖、侵袭和转移能力;蛋白质印迹法(Western blot)检测调控LINC01235的表达对磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶蛋白(mTOR)信号通路的影响。应用SAS 9.4软件进行统计学分析,t检验分析实验结果。结果TCGA数据分析表明与癌旁组织比较,LINC01235在胃癌组织中的表达水平高于癌旁组织(6.340±1.705比3.115±1.558,Z=10.026,P<0.05),且LINC01235高表达的患者预后较差(χ^(2)=6.902,P<0.05)。临床标本验证结果与生物信息学结果相符。蛋白质印迹结果显示,胃癌组织中PI3K/Akt/mTOR信号通路中磷酸化蛋白激酶B(p-Akt)、磷酸化雷帕霉素靶(p-mTOR)的表达水平高于癌旁组织(p-Akt为1.154±0.459比0.326±0.150,t=9.392,P<0.01;p-mTOR为0.665±0.310比0.270±0.121,t=6.501,P<0.01)。在MGC-803细胞中上调LINC01235后细胞的增殖能力显著比对照组增强(24 h为0.203±0.027比0.142±0.042,t=2.993,P<0.05;48 h为0.503±0.106比0.247±0.064,t=5.064,P<0.01;72 h为0.917±0.118比0.55±0.11,t=5.573,P<0.01)、侵袭和转移能力显著比对照组增强(139.333±22.151比57.833±15.639,t=-7.362,P<0.01;111.667±15.016比73.667±14.024,t=-4.530,P<0.01);在SGC-7901细胞中抑制LINC01235的表达后细胞的增殖能力显著比对照组降低(48 h为0.425±0.133比0.667±0.091,t=-3.678,P<0.01;72 h为0.565±0.157比0.945±0.200,t=-3.661,P<0.01)、侵袭和转移能力显著比对照组降低(50.667±13.231比141.167±15.224,t=10.991,P<0.01;57.667±14.348比166.167±25.631,t=9.048,P<0.01)。在MGC-803细胞中上调LINC01235表达后p-Akt、p-mTOR、细胞周期蛋白E1(Cyclin E1)表达比对照组增强(p-Akt为0.851±0.138比0.366±0.138,Objective To explore the expression of long non-coding RNA LINC01235 in gastric cancer and related molecular mechanism.Methods The cancer genome atlas(TCGA)database was used to detect the expression of LINC01235 in gastric cancer and adjacent tissues.The prognostic value of LINC01235 in patients with gastric cancer was analyzed.Fresh gastric cancer and adjacent tissues were collected to verify the bioinformatics results.The expression of LINC01235 in human gastric cancer cell lines MGC-803 and SGC-7901 was regulated to detect cell proliferation,invasion and metastasis.Western blotting was applied to detect the effect of LINC01235 on phosphoinositide-3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.T test was applied for statistical analysis using SAS 9.4.Results TCGA data analysis showed that as compared with adjacent tissues,LINC01235 was highly expressed in gastric cancer tissues(6.340±1.705 vs.3.115±1.558,Z=10.026,P<0.05).The patients with high expression of LINC01235 had a poorer prognosis(χ^(2)=6.902,P<0.05).Results of clinical specimens were consistent with the bioinformatics results.Western blotting results showed that the expression levels of p-Akt and p-mTOR in the PI3K/Akt/mTOR signaling pathway in gastric cancer tissues were significantly higher than those in adjacent tissues(for p-Akt,1.154±0.459 vs.0.326±0.150,t=9.392,P<0.01;for p-mTOR,0.665±0.310 vs.0.270±0.121,t=6.501,P<0.01).After up-regulating LINC01235 in MGC-803 cells,the cell proliferation ability was significantly enhanced as compared with than in the control group(at 24 h,0.203±0.027 vs.0.142±0.042,t=2.993,P<0.05;at 48 h,0.503±0.106 vs.0.247±0.064,t=5.064,P<0.01;at 72 h,0.917±0.118 vs.0.55±0.11,t=5.573,P<0.01),invasion and metastasis ability was significantly enhanced as compared with that in the control group(139.333±22.151 vs.57.833±15.639,t=-7.362,P<0.01;111.667±15.016 vs.73.667±14.024,t=-4.530,P<0.01).After up-regulating the expression of LINC01235 in MGC-803 cells,the expression

关 键 词：胃癌 长链非编码RNA 磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路 

分 类 号：R735.2[医药卫生—肿瘤]