circDIDO1通过miR-141/Keap-Nrf2/HO-1通路对人卵巢癌细胞株SKOV3增殖、侵袭和迁移的影响  

The effect of circDIDO1 on proliferation,invasion and migration of human ovarian cancer cell line SKOV3 through miR-141/Keap-Nrf2/HO-1 pathway

作　　者：郭明秋[1] 辛晓妮[1] 刁殿琰[1] GUO Mingqiu;XIN Xiaoni;DIAO Dianyan(Qingdao Municipal Hospital,Qingdao,Shandong 266000,China)

机构地区：[1]青岛市市立医院,山东青岛266000

出　　处：《中国优生与遗传杂志》2023年第10期2008-2013,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目的 探讨环状非编码RNA(circ)DIDO1通过微小RNA(miR)-141/Kelch样环氧氯丙烷相关蛋白-1(Keap1)-核因子E2相关因子2(Nrf2)/血红素氧合酶-1(HO-1)通路探讨对人卵巢癌细胞株SKOV3增殖、侵袭和迁移的影响。方法 qRT-PCR检测卵巢癌组织及细胞系(SKOV3、OVCAR3和A2780)及IOSE80细胞中miR-141、circDIDO1、Keap1、Nrf2、HO-1 mRNA表达水平;取SKOV3细胞,设置分组为对照组、DIDO1过表达(Exo-circDIDO1)组(转染Exo-circDIDO1)、过表达阴性对照(Exo-vector)组(转染Exo-vector)、Exo-circDIDO1+miR-141模拟物(miR-141mimics)组(共转染Exo-circDIDO1、miR-141mimics)、Exo-circDIDO1+模拟物阴性对照(mimicsNC)组(共转染Exo-circDIDO1、mimicsNC)。48h后,CCK-8及Transwell实验检测细胞迁移、侵袭及增殖变化;qRT-PCR检测及Westernblot检测各组细胞miR-141、circDIDO1、Keap1、Nrf2、HO-1表达;双荧光素酶验证miR-141分别与circDIDO1、Keap1靶向关系。结果 与IOSE80细胞及正常组织相比,SKOV3、OVCAR3和A2780细胞及癌组织中circDIDO1、Keap1 mRNA表达显著降低,miR-141、Nrf2、HO-1 mRNA表达显著增加(P<0.05),以SKOV3细胞中变化最为显著。miR-141分别与Keap1、circDIDO1均为靶向关系。与对照组、Exo-vector组相比,Exo-circDIDO1组circDIDO1、Keap1蛋白及mRNA表达显著增加,细胞增殖率及细胞侵袭、迁移数、miR-141、Nrf2、HO-1蛋白及mRNA显著下降(P<0.05),miR-141 mimics逆转了Exo-circDIDO1对SKOV3细胞恶性行为的抑制作用。结论 过表达circDIDO1可通过调控miR-141/Keap-Nrf2/HO-1通路阻止人卵巢癌细胞株SKOV3增殖、侵袭和迁移。Objective To investigate the effect of circDIDO1 on proliferation,invasion and migration of human ovarian cancer cell line SKOV3 through miR-141/Keap-Nrf2/HO-1 pathway.Methods The expression of miR-141,circDIDO1,Keap1,Nrf2 and HO-1 mRNA in ovarian cancer tissue,cell lines(SKOV3,OVCAR3 and A2780)and IOSE80 cells was detected by qRT-PCR.SKOV3 cells were taken and grouped into control group,DIDO1 overexpression(Exo-circDIDO1)group(transfected with Exo-circDIDO1),overexpression negative control(Exo-vector)group(transfected with Exo-vector),Exo-circDIDO1+miR-141 mimics group(co-transfected with Exo-circDIDO1 and miR-141 mimics),and Exo-circDIDO1+mimics negative control(mimics NC)group(co-transfected with Exo-circDIDO1 and mimics NC).After 48 hours,Cell migration,invasion and proliferation were detected by CCK-8 and Transwell assay.The expressions of miR-141,circDIDO1,Keap1,Nrf2 and HO-1 were detected by qRT-PCR and Western blot,and double luciferase was applied to verify the targeting relationship between miR-141 and circDIDO1 and Keap1,respectively.Results Compared with IOSE80 cells and normal tissue,the expression of circDIDO1 and Keap1 mRNA in SKOV3,OVCAR3 A2780 cells and cancer tissue decreased obviously,the expression of miR-141,Nrf2 and HO-1 mRNA increased obviously(P<0.05),the most obvious change was in SKOV3 cells.miR-141 was targeted to Keap1 and circDIDO1 respectively.Compared with the control group and the Exo-vector group,the expression of circDIDO1,Keap1 protein and mRNA in the Exo-circDIDO1 group increased obviously,the cell proliferation rate,the numbers of cell invasion and migration,miR-141,Nrf2,HO-1 protein and mRNA decreased obviously(P<0.05).miR-141 mimics reversed the inhibitory effect of Exo-circDIDO1 on the malignant behavior of SKOV3 cells.Conclusion Overexpression of circDIDO1 can inhibit the proliferation,invasion and migration of human ovarian cancer cell line SKOV3 by regulating miR-141/Keap-Nrf2/HO-1 pathway.

关 键 词：人卵巢癌细胞株SKOV3 circDIDO1 增殖 侵袭和迁移 

分 类 号：R737.31[医药卫生—肿瘤]