lncRNA MAGI2-AS3调节miR-218-5p/KDM2A轴对宫颈癌细胞活性和上皮间质转化的影响  

Effect of lncRNA MAGI2-AS3 on the activity and epithelial mesenchymal transition of cervical cancer cells by regulating the miR-218-5p/KDM2A axis

作　　者：贲崴[1] 李扬[1] 罗佳玲 单铁虎 BEN Wei;LI Yang;LUO Jialing;SHAN Tiehu(Department of Obstetrics and Gynecology,The First Affiliated Hospital of Harbin Medical University,Harbin,Heilongjiang 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院妇产科,黑龙江哈尔滨150001

出　　处：《中国优生与遗传杂志》2024年第8期1545-1551,共7页Chinese Journal of Birth Health & Heredity

基　　金：哈医大一院科研创新基金面上项目(2021M01)。

摘　　要：目的探讨lncRNA MAGI2-AS3调节miR-218-5p/赖氨酸去甲基化酶2A(KDM2A)轴对宫颈癌(CC细胞活性)和上皮间质转化(EMT)的影响。方法将体外培养的CaSki细胞分为NC组、si-NC组、si-MAGI2-AS3组、miR-NC组、miR-218-5p mimic组、si-MAGI2-AS3+inhibitor NC组、si-MAGI2-AS3+miR-218-5p inhibitor组。检测MAGI2-AS3、miR-218-5p、KDM2AmRNA在CC组织、不同细胞及各组CaSki细胞中的表达水平;检测CaSki细胞增殖、迁移、侵袭、凋亡、Bax、Bcl-2及EMT相关蛋白表达;双荧光素酶实验验证miR-218-5p与MAGI2-AS3、KDM2A的关系。结果CC组织中MAGI2-AS3、KDM2AmRNA表达高于癌旁组织,miR-218-5p低于癌旁组织(P<0.05)。HcerEpic细胞、C-33A细胞、CaSki细胞中MAGI2-AS3、KDM2A mRNA表达均依次升高,miR-218-5p依次降低(P<0.05)。si-MAGI2-AS3组MAGI2-AS3、KDM2AmRNA表达、CaSki细胞增殖率、迁移率、侵袭细胞数、Bcl-2、Vimentin表达均低于NC组和si-NC组,miR-218-5p表达、CaSki细胞凋亡率、Bax、E-cadherin表达均高于NC组和si-NC组(P<0.05);miR-218-5pmimic组KDM2AmRNA表达、CaSki细胞增殖率、迁移率、侵袭细胞数、Bcl-2、Vimentin表达均低于miR-NC组,miR-218-5p表达、CaSki细胞凋亡率、Bax、E-cadherin表达均高于miR-NC组(P<0.05)。双荧光素酶报告基因实验显示miR-218-5p和MAGI2-AS3、KDM2A均存在靶向调控关系(P<0.05)。结论MAGI2-AS3在CC细胞中呈高表达,下调MAGI2-AS3可调节miR-218-5p/KDM2A轴抑制CaSki细胞恶性生物学行为,诱导其凋亡。Objective To investigate the effect of lncRNA MAGI2-AS3 on the activity and epithelial mesenchymal transition(EMT)of cervical cancer(CC)cells by regulating the miR-218-5p/lysine demethylase 2A(KDM2A)axis.Methods CaSki cells cultured in vitro were separated into NC group,si-NC group,si-MAGI2-AS3 group,miR-NC group,miR-218-5p mimic group,si-MAGI2-AS3+inhibitor NC group,and si-MAGI2-AS3+miR-218-5p inhibitor group.To detect the expression levels of MAGI2-AS3,miR-218-5p,and KDM2A mRNA in CC tissue,different cells,and CaSki cells in each group.To detect CaSki cell proliferation,migration,invasion,apoptosis,Bax,Bcl-2,and EMT related proteins.Dual luciferase assay was applied to verify the relationship between miR-218-5p and MAGI2-AS3,KDM2A.Results The mRNA expression of MAGI2-AS3 and KDM2A in CC tissue was higher than that in adjacent cancer tissue,and miR-218-5p was lower than that in adjacent cancer tissue(P<0.05).The mRNA expression of MAGI2-AS3 and KDM2A in HcerEpic cells,C-33A cells,and CaSki cells increased sequentially,while miR-218-5p decreased sequentially(P<0.05).The mRNA expression of MAGI2-AS3 and KDM2A,CaSki cell proliferation rate,migration rate,number of invasive cells,expression of Bcl-2 and Vimentin in the si-MAGI2-AS3 group were lower than those in the NC and si-NC groups,the expression of miR-218-5p,CaSki cell apoptosis rate,expression of Bax and E-cadherin were higher than those in the NC group and si-NC group(P<0.05).The mRNA expression of KDM2A,CaSki cell proliferation rate,migration rate,number of invasive cells,expression of Bcl-2 and Vimentin in the miR-218-5p mimic group were lower than those in the miR-NC group,the expression of miR-218-5p,CaSki cell apoptosis rate,expression of Bax and E-cadherin were higher than those in the miR-NC group(P<0.05).Dual luciferase reporter gene experiment revealed a targeted regulatory relationship between miR-218-5p,MAGI2-AS3,and KDM2A(P<0.05).Conclusion MAGI2-AS3 was highly expressed in CaSki cell,and downregulation of MAGI2-AS3 regulated the miR-218-5p/KDM2A

关 键 词：MAGI2-AS3 miR-218-5p 赖氨酸去甲基化酶2A 宫颈癌 上皮间质转化 

分 类 号：R737.33[医药卫生—肿瘤]