TRIM11靶向调控miR-24-3p促进乳腺癌细胞系MCF7增殖和侵袭  

TRIM11 promotes proliferation and invasion of breast cancer cell line MCF7 by targeting miR-24-3p

作　　者：张洋[1] 张静[1] 季琳[2] 李文媛[1] 王莹[1] 孙平[1] 于伟光[3] ZHANG Yang;ZHANG Jing;JI Lin;LI Wenyuan;WANG Ying;SUN Ping;YU Weiguang(Dept.of Anatomy,Mudanjiang Medical College,Mudanjiang157011,China;Dept.of Biochemistry and Molecular Biology,Mudanjiang Medical College,Mudanjiang157011,China;Dept.of Surgery,Hongqi Hospital,Mudanjiang Medical College,Mudanjiang157011,China)

机构地区：[1]牡丹江医学院解剖教研室,黑龙江牡丹江157011 [2]牡丹江医学院生物化学与分子生物学教研室,黑龙江牡丹江157011 [3]牡丹江医学院红旗医院普外一科,黑龙江牡丹江157011

出　　处：《基础医学与临床》2018年第4期451-457,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金(81371362);黑龙江省自然科学基金(H201377)

摘　　要：目的探讨TRIM11靶向调控miR-24-3p对乳腺癌细胞增殖和侵袭的影响,明确TRIM11高表达与乳腺癌预后的相关性。方法免疫组化法检测TRIM11在31例乳腺癌和31例癌旁正常组织中的表达。用siRNA TRIM11和miR-24-3p慢病毒转染人乳腺癌MCF7细胞,实时荧光定量PCR(RT-q PCR)和Western bolt检测TRIM11、miR-24-3p mRNA和蛋白表达变化及相关性分析;荧光素酶报告实验验证miR-24-3p为TRIM11的潜在靶点;MTT法和Transwell检测细胞增殖数量、增殖活力和侵袭。结果 TRIM11在乳腺癌组织及MCF7细胞中表达显著增高(P<0.05)。TRIM11高表达患者生存率显著降低(P<0.05)。siRNA TRIM11转染显著抑制MCF7细胞中TRIM11表达,而且抑制MCF7细胞增殖数量、增殖活力和侵袭能力(P<0.05)。miR-24-3p显著降低野生型3'-UTR TRIM11荧光素酶活性(P<0.05),但对突变型没有作用。miR-24-3p mRNA在MCF7细胞下调,miR-24-3p抑制MCF7细胞TRIM11蛋白和mRNA表达,miR-24-3p mRNA与TRIM11 mRNA在MCF7细胞中表达显著负相关(P<0.05),miR-24-3p抑制MCF7细胞增殖数量、增殖活力和侵袭能力(P<0.05)。结论 TRIM11在乳腺癌组织及MCF7细胞中表达上调,并可能通过靶向调控miR-24-3p促进乳腺癌细胞增殖和侵袭,进而影响乳腺癌预后,TRIM11/miR-24-3p轴有望成为治疗乳腺癌的新靶点。Objective To investigate the effect of TRIM11(tripartite motif-containing protein 11)target regulating miR-24-3p on the proliferation and invasion of breast cancer cells,and potentiol relation between TRIM11 high expression and the prognosis of breast cancer.Methods Immunohistochemical method was used to detect the expression of TRIM11 in 31 cases of breast cancer and 31 cases of adjacent breast cancer normal tissues.The siRNA TRIM11 lentivirus and miR-24-3p lentivirus were transfected into human breast cancer MCF7 cell lines,observing the correlation expression of TRIM11 and miR-24-3p mRNA and protein by using real-time fluorescence quantitative PCR(RT-qPCR)and Western bolt,luciferase reporter experiments were used to verify that the miR-24-3p as a direct target of TRIM11,MTT and Transwell were used to investigate the cells proliferation,activity and invasion.Results The expression of TRIM11 in breast cancer tissues or MCF7 cells was significantly higher(P<0.05),and TRIM11 high expression predicts poor prognosis of breast cancer(P<0.05).siRNA TRIM11 significantly inhibited the expression of TRIM11 in MCF7 cells,moreover,which inhibited the MCF7 cells proliferation,viability and invasion(P<0.05).miR-24-3p significantly reduced 3′-UTR TRIM11 luciferase activity in wild-type(P<0.05),but no effect was found in mutant type.The expression of miR-24-3p was decreased,miR-24-3p and TRIM11 mRNA expression was negatively correlated in MCF7 cells(P<0.05),miR-24-3p inhibition protein and mRNA expression of TRIM11 in MCF7 cells,and inhibit MCF7 cells proliferation,viability and invasion(P<0.05).Conclusions The expression of TRIM11 is up-regulated in breast cancer and cells,promote the proliferation and invasion of breast cancer cells though regulating miR-24-3p expression,TRIM11 high expression predicts poor prognosis of breast cancer,TRIM11/miR-24-3p axis is expected to become a new target for treatment of breast cancer.

关 键 词：TRIM11 miR-24-3p 乳腺癌 增殖 侵袭 

分 类 号：R735[医药卫生—肿瘤]