miR-876-5p通过靶向FOXM1对儿童髓母细胞瘤细胞增殖的影响  

Mir⁃876⁃5p suppressed the proliferation of pediatric medulloblastoma cells through targeting fork⁃head box M1

作　　者：吴水华[1] 张津维 陈朝晖[1] 伍添 苏君 王海阳 Wu Shuihua;Zhang Jinwei;Chen Zhaohui;Wu Tian;Su Jun;Wang Haiyang(Department of Neurosurgery,Hunan Children's Hospital,Changsha 410007,China;Department of Neurosurgery,Hainan Women&Children's Medical Center,Haikou 570312,China)

机构地区：[1]湖南省儿童医院神经外科,长沙410007 [2]海南省妇女儿童医学中心神经外科,海口570312

出　　处：《中华小儿外科杂志》2022年第5期385-390,共6页Chinese Journal of Pediatric Surgery

基　　金：湖南省出生缺陷协同防治科技重大专项(2019SK1010)。

摘　　要：目的探讨微小核糖核酸876-5p(micro ribonucleic acid-876-5p,miR-876-5p)通过靶向叉头盒蛋白M1(forkhead box M1,FOXM1)对儿童髓母细胞瘤(medulloblastoma,MB)细胞增殖的影响。方法收集2018年1月至2020年10月在湖南省儿童医院进行手术治疗的30例MB患儿临床资料,其中男21例,女9例,年龄为(10.42±2.17)岁,范围为5~14岁。通过qPCR检测肿瘤组织和癌旁组织标本中miR-876-5p和FOXM1、TAp73、Beclin1、Livin、Cyclin D1在mRNA水平的表达情况;通过CCK8和Transwell实验观察过表达miR-876-5p后对MB细胞的增殖和侵袭能力的影响;通过qPCR和WB实验检测过表达miR-876-5p前后,FOXM1、TAp73、Beclin1、Livin、Cyclin D1在蛋白或mRNA水平表达的变化。结果miR-876-5p在MB中表达显著降低(P<0.001),过表达miR-876-5p能够显著抑制MB细胞的增殖和侵袭能力(P<0.01)。FOXM1在MB中表达上调,其表达与miR-876-5p呈负相关(r=‒0.527,P=0.013)。在MB细胞中过表达miR-876-5p能够抑制FOXM1的表达。此外,在MB中,miR-876-5p的表达与TAp73和Beclin1呈正相关(r=0.506,P=0.008;r=0.535,P=0.003),与Livin和Cyclin D1 mRNA呈负相关(r=‒0.496,P=0.011;r=‒0.574,P=0.005)。与之相反,FOXM1的表达与TAp73和Beclin1呈负相关(r=‒0.554,P=0.007;r=‒0.497,P=0.016),与Livin和Cyclin D1呈正相关(r=0.502,P=0.009;r=0.476,P=0.015)。此外,miR-876-5p在MB细胞中可以下调Livin和Cyclin D1的表达,上调TAp73在Beclin1的表达。结论miR-876-5p具有抑制MB增殖和侵袭的作用,而FOXM1可能促进MB增殖和侵袭。miR-876-5p可能通过靶向调控FOXM1促进机体内抑癌基因的表达并抑制致癌基因表达,最终抑制MB细胞增殖和侵袭。Objective To explore the mechanism of microRNA 876-5p(miR-876-5p)suppressing the proliferation and invasion of medulloblastoma(MB)cells by targeting forkhead box M1(FOXM1).Methods From January 2018 to October 2020,clinical data were retrospectively reviewed for 30 surgical MB children at Hunan Childrens Hospital.There were 21 boys and 9 girls with an average age of(10.42±2.17)(5-14)years.The expressions of miR-876-5p,FOXM1 mRNA,TAp73mRNA,Beclin1 mRNA,Livin mRNA and Cyclin D1 mRNA were detected by quantitative polymerase chain reaction(qPCR)in MB and normal tissues.The effects of miR-876-5p over-expression on cellular proliferation and invasion were observed by CCK8 and Transwell assays.And the expressions of FoxM1,TAp73,Beclin1,Livin and Cyclin D1 were detected by qPCR or WB with or without mir-876-5p over-expression.Results The expression of mir-876-5p dropped markedly in MB tissue(P<0.001).And over-expression of miR-876-5p could significantly suppress cellular proliferation and invasion(P<0.01).FOXM1 was up-regulated in MB tissue and its expression was negatively correlated with miR-876-5p(r=‒0.527,P=0.013).Furthermore,miR-876-5p could lower the expression of FOXM1.Moreover,the expression of miR-876-5p was correlated positively with the expressions of TAp73(r=0.506,P=0.008)and Beclin1(r=0.535,P=0.003)and negatively with the expressions of Livin(r=‒0.496,P=0.011)and Cyclin D1(r=‒0.574,P=0.005).Inversely FOXM1 expression was correlated negatively with the expressions of TAp73(r=‒0.554,P=0.007)and Beclin1(r=‒0.497,P=0.016)and positively with the expressions of Livin(r=0.502,P=0.009)and Cyclin D1(r=0.476,P=0.015).Also miR-876-5p could down-regulate the expressions of Livin and Cyclin D1 and up-regulate the expression of TAp73 in Beclin1.Conclusion miR-876-5p can suppress cellular proliferation and invasion.However,FoxM1 may promote cellular proliferation and invasion.And miR-876-5p may promote the expression of tumor suppressor genes and reduce the expression of oncogenes by targeting FOXM1 and ultimatel

关 键 词：髓母细胞瘤 叉头转录因子类 微小RNA 细胞增殖 

分 类 号：R739.4[医药卫生—肿瘤]