microRNA-487a靶向MAGI2对肾癌细胞迁移和侵袭的影响  

Effects of microRNA-487a targeting MAGI2 on cell migration and invasion in renal cell carcinoma

作　　者：许晖阳 陈波特[1] 邱晓拂[1] XU Huiyang;CHEN Bote;QIU Xiaofo(Department of Urology,Guangdong Second Provincial General Hospital,Guangzhou 510317,China)

机构地区：[1]广东省第二人民医院泌尿外科,广州510317

出　　处：《临床肿瘤学杂志》2025年第2期119-124,共6页Chinese Clinical Oncology

摘　　要：目的探讨miR-487a在肾细胞癌增殖、迁移和侵袭中的潜在作用。方法采用实时荧光定量PCR(qRT-PCR)检测人肾癌细胞系(786-O、ACHN、Caki-1、Caki-2)和永生化正常人肾近端小管上皮细胞系HK-2中miR-487a的表达。将786-O肾癌细胞分为3组:NC组(转染miR-487a阴性对照)、Control组(空白对照)和miR-487a inhibitor组(转染miR-487a抑制剂)。CCK-8法检测miR-487a对786-O细胞增殖的影响;伤口愈合实验和Transwell小室实验检测肾癌细胞786-O的迁移和侵袭能力;荧光素酶报告实验分析miR-487a与MAGI2的靶向关系;qRT-PCR和Western blotting检测MAGI2、MMP-9和Smad4的表达。结果与HK-2细胞相比,miR-487a在肾癌细胞系Caki-2、ACHN、Caki-1和786-O中的表达水平显著上调(P<0.05)。与Control组相比,786-O肾癌细胞转染miR-487a inhibitor 48 h和72 h后的增殖能力下降,差异有统计学意义(P<0.05);与NC组相比,miR-487a inhibitor组的细胞迁移数目(25.847±3.126 vs.76.533±4.243)和穿膜细胞数目(101.600±13.741 vs.274.200±54.348)显著减少,差异有统计学意义(P<0.05)。MAGI2是miR-487a的直接靶点。与NC组相比,miR-487a inhibitor组MAGI2和Smad4表达增加、MMP-9表达降低(P<0.05)。结论miR-487a可以靶向调控MAGI2并抑制Smad4表达,在人肾癌中发挥促癌因子的作用。Objective To explore the role of miR-487a in proliferation,migration and invasion in renal cell carcinoma.Methods The expression of miR-487a in human renal cancer cell lines(786-O,ACHN,Caki-1,and Caki-2)and immortalized normal human proximal tubule epithelial cell line HK-2 was detected by quantitative real-time PCR(qRT-PCR).786-O renal cancer cells were divided into three groups:NC group(transfected with miR-487a negative control),Control group(blank control),and miR-487a inhibitor group(transfected with miR-487a inhibitor).The effects of miR-487a on the proliferation of 786-O cell was evaluated by CCK-8.Wound-healing and Transwell assays were used to examine the migration and invasion abilities of renal cell carcinoma cells.The targeting relationship between miR-487a and MAGI2 was explored using luciferase reporter analysis.The expressions of MAGI2,MMP-9 and Smad4 were detected by qRT-PCR and western blotting analysis.Results Compared with HK-2 cell,miR-487a was up-regulated in renal cancer cell Caki-2,ACHN,Caki-1 and 786-O(P<0.05).Compared with the control group cells,the proliferation ability of 786-O renal cancer cells transfected with miR-487a inhibitor after 48 and 72 hours were decreased,and the difference was statistically significant(P<0.05).Compared with the NC group,the number of cell migration(25.847±3.126 vs.76.533±4.243)and the number of transmembrane cells(101.600±13.741 vs.274.200±54.348)in the miR-487a inhibitor group were significantly reduced(P<0.05).MAGI2 may be a target gene of miR-487a.Compared with NC group,the expressions of MAGI2 and Smad4 were promoted,while MMP-9 was reduced in miR-487a inhibitor group(P<0.05).Conclusion miR-487a can target MAGI2,inhibit Smad4 expression,and function as a tumor promoter in human renal cancer.

关 键 词：肾细胞癌 miR-487a 侵袭 迁移 MAGI2 SMAD4 

分 类 号：R737.1[医药卫生—肿瘤]