miR-198靶向抑制FGFR1表达抑制胃癌细胞增殖并诱导细胞凋亡  

Targeted inhibition of miR-198 on the FGFR1 expression for inhibiting the proliferation and inducing apoptosis of gastric cancer cells

作　　者：莎比亚·沙吾提 雷云霞[1] 热娜古丽·艾则孜[2] SHABIYA Sha-wuti;LEI Yun-xia;GENNA Guri-aziz(Department of Spleen and Stomach Diseases,Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University,Urumchi 830000,China.)

机构地区：[1]新疆医科大学附属中医医院脾胃病科新疆,乌鲁木齐830000 [2]新疆医科大学附属中医医院肿瘤一科,新疆乌鲁木齐830000

出　　处：《中国医学装备》2021年第6期178-183,共6页China Medical Equipment

基　　金：新疆维吾尔自治区自然科学基金(2018D12C169)“miR-198通过靶向抑制FGFR1表达对胃癌的生物学功能研究”。

摘　　要：目的:探究微小RNA(miR)-198对胃癌细胞增殖及凋亡的影响及其可能的作用机制。方法:培养人胃癌细胞株系MKN-45、SGC-7901和BGC-823以及人胃黏膜上皮细胞(GES-1),采用实时荧光定量聚合酶链反应(RT-qPCR)检测miR-198在胃癌细胞中的表达;对胃癌细胞MKN-45进行miR-198模拟物(mimic)和阴性对照(mimiccontrol)转染,分别设定为miR-198 mimic+control组和miR-198 mimic+FGFR1组,采用细胞计数试剂盒-8(CCK-8)和流式细胞仪检测miR-198表达上调对胃癌细胞增殖和凋亡的影响。采用生物信息学网站预测miR-198的潜在靶基因;采用双荧光素酶报告实验及免疫印迹(Western Blot)验证miR-198对成纤维细胞生长因子受体1(FGFR1)的调控关系。结果:与GES-1细胞相比,miR-198在MKN-45、SGC-7901和BGC-823胃癌细胞中的表达显著下调,差异有统计学意义(t=35.068,t=9.872,t=20.585;P<0.01);miR-198表达上调显著抑制胃癌细胞的增殖,两组细胞在转染第48 h和72 h增殖比较和诱导细胞凋亡比较,差异均有统计学意义(t_(增殖)=5.041,t=6.041;t_(凋亡)=6.797;P<0.01);WesternBlot实验中,miR-198 mimic组FGFR1蛋白水平与mimic control组相比,显著抑制了FGFR1蛋白水平表达,差异有统计学意义(t=6.030,P<0.01);CCK-8实验中miR-198mimic组+FGFR1细胞增殖能力明显增强,细胞凋亡率显著降低,与miR-198 mimic+control组相比,差异有统计学意义(t=4.797,t=7.249;P<0.01)。结论:miR-198通过靶向抑制FGFR1的表达而抑制胃癌细胞的增殖,诱导细胞凋亡,在胃癌中发挥抑癌基因功能。Objective:To investigate the effect of microRNA(miR-198)on the proliferation and apoptosis of gastric cancer cells and the possible mechanism of that.Methods:Human gastric cancer cell strains included MKN-45,SGC-7901 and BGC-823 and human gastric mucosal epithelial cell(GES-1)were cultured,and the expression of miR-198 in gastric cancer cell was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).MKN-45 of gastric cancer cells were transfected with miR-198 simulant(mimic)and negative control(mimic control).And they were significantly set as miR-198 mimic group and mimic control group.The effects of miR-198 expression upregulation on proliferation and apoptosis of gastric cancer cells were detected by cell counting kit(CCK-8)and flow cytometry.The bioinformatics website was adopted to predict potential target gene of miR-198,and report experiment of dual-luciferase and Western blot were adopted to verify the regulated relation of miR-198 on fibroblast growth factor receptors-1(FGFR1).Results:Compared with human(GES-1),miR-198 expression was significantly down-regulated in other three kinds of gastric cancer cells,and the differences of that among them were significant(t=35.068,t=9.872,t=20.585,P<0.01).The up-regulated expression of miR-198 significantly inhibited the proliferation of gastric cancer cells,and the differences of proliferation and induced apoptosis at the 48th h and 72th h post transfection between two groups were significant(tproliferation=5.041,t=6.041,tapoptosis=6.797,P<0.01).In Western Blot experiment,the FGFR1 level of miR-198 mimic group was significantly inhibited,and the difference of that between the two groups was significant(t=6.030,P<0.01).In CCK-8 experiment,the ability of cell proliferation of miR-198 mimic+FGFR1 group was significantly increased and the apoptosis rate of that was significantly decreased,and the differences of those between that and miR-198 mimic control group were significant(t=4.797,t=5.827,P<0.01).Conclusion:miR-198 can inhibit the prol

关 键 词：微小RNA-198(miR-198) 胃癌 成纤维细胞生长因子受体1(FGFR1) 增殖 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]