miR-433-3p通过靶向SMC4抑制IL-17对肺癌细胞增殖、迁移、侵袭的促进作用  

miR-433-3p inhibits IL-17 mediated proliferation, migration, and invasion of lung cancer cells by targeting SMC4

作　　者：井洪家 刘建伟[1] 马建欣[1] 李晓峰[1] 齐迎松 JING Hong-jia;LIU Jian-wei;MA Jian-xin;LI Xiao-feng;QI Ying-song(Cardiothoracic Surgery,Chengde Central Hospital,Chengde 067000,China)

机构地区：[1]承德市中心医院心胸外科,承德067000

出　　处：《现代免疫学》2022年第6期489-498,共10页Current Immunology

基　　金：河北省卫计委医学科学研究重点课题计划(20160298)。

摘　　要：为探讨IL-17对肺癌细胞增殖、迁移和侵袭的作用机制,用IL-17(20 ng/mL)处理肺癌细胞A549和HCC827 48 h,采用Western blotting、qRT-PCR、Transwell试验、MTT试验和双荧光素酶报告基因试验分别检测A549和HCC827细胞中细胞周期素D1(Cyclin D1)、基质金属蛋白酶2(matrix metalloproteinase 2,MMP-2)、基质金属蛋白酶9(matrix metallopro-teinase 9,MMP-9)、细胞周期蛋白依赖性激酶抑制蛋白(cyclin-dependent kinase inhibitor protein, p21)、染色体结构维持蛋白4(structural maintenance of chromosome 4,SMC4)的蛋白表达,miR-433-3p、SMC4的mRNA表达,细胞的增殖、迁移和侵袭及细胞的荧光素酶活性。结果显示,与对照组比较,IL-17组A549和HCC827细胞的增殖、迁移和侵袭能力均显著升高(P<0.05),miR-433-3p表达水平显著下调(P<0.05),SMC4表达水平显著上调(P<0.05),同时Cyclin D1、MMP-2、MMP-9水平显著上调(P<0.05);miR-433-3p与SMC4存在结合位点;分别与anti-miR-NC组、pcDNA组比较,anti-miR-433-3p组、pcDNA-SMC4组A549和HCC827细胞的增殖、迁移和侵袭能力显著升高(P<0.05),同时Cyclin D1、MMP-2、MMP-9水平显著上调(P<0.05);miR-433-3p可抑制IL-17诱导的细胞增殖、迁移和侵袭的能力,并下调Cyclin D1、MMP-2、MMP-9水平。该研究提示,IL-17助力于肺癌细胞的增殖、迁移和侵袭,其机制可能与抑制miR-433-3p/SMC4通路的活性相关。The goal of this study is to investigate the mechanism of IL-17 on the proliferation, migration, and invasion of lung cancer cells. A549 and HCC827 lung cancer cells were treated with IL-17(20 ng/mL) for 48 h and Western blotting, qRT-PCR, Transwell analysis, MTT analysis, and dual luciferase reporter gene experiments were performed respectively to detect the protein levels of Cyclin D1, matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), cyclin-dependent kinase inhibitor protein(p21) and structural maintenance of chromosome 4(SMC4);the mRNA expression of miR-433-3 p and SMC4;cell proliferation, migration, invasion, and luciferase activity of the two cancer cells lines. The results showed that compared with the control group, the proliferation, migration, and invasion of A549 and HCC827 cells in the IL-17-treated groups were significantly increased(P<0.05), while the expression level of miR-433-3 p was significantly decreased(P<0.05). Meanwhile, the expressions of SMC4, Cyclin D1, MMP-2, and MMP-9 were all up-regulated(P<0.05). miR-433-3 p had a binding site with SMC4. Compared with the anti-miR-NC group and the pcDNA group, the proliferation, migration, and invasion abilities of A549 and HCC827 cells in the anti-miR-433-3 p group and the pcDNA-SMC4 group were significantly increased(P<0.05). At the same time, the levels of Cyclin D1, MMP-2, and MMP-9 were significantly up-regulated(P<0.05). Therefore, miR-433-3 p may inhibit IL-17-induced cell proliferation, migration, and invasion, and downregulate the levels of Cyclin D1, MMP-2, and MMP-9. Together, this study suggests that IL-17 contributes to the proliferation, migration, and invasion of lung cancer cells, possibly by inhibiting the activity of the miR-433-3 p/SMC4 pathway.

关 键 词：白细胞介素17 微小RNA-433-3p 染色体结构维持蛋白4 肺癌 增殖 迁移 侵袭 

分 类 号：R734.2[医药卫生—肿瘤]