紫甘薯花色苷通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭  

Purple sweet potato anthocyanin regulates the proliferation,migration and invasion of breast cancer MDA-MB-231 cells through circ_0003998/miR-145 axis

作　　者：马建萍 宋连川 赵成茂 吕永 李华 汪学昌 MA Jianping;SONG Lianchuan;ZHAO Chengmao;LYU Yong;LI Hua;WANG Xuechang(Department of Breast Medicine,the Fifth People's Hospital of Qinghai Province,Xining 810000,Qinghai,China;Department of Pathology,the Fifth People's Hospital of Qinghai Province,Xining 810000,Qinghai,China;Department of Radiotherapy,the Fifth People's Hospital of Qinghai Province,Xining 810000,Qinghai,China)

机构地区：[1]青海省第五人民医院乳腺科,青海西宁810000 [2]青海省第五人民医院病理科,青海西宁810000 [3]青海省第五人民医院放疗科,青海西宁810000

出　　处：《中国肿瘤生物治疗杂志》2021年第7期672-679,共8页Chinese Journal of Cancer Biotherapy

基　　金：青海省卫生计生系统科研课题资助项目(No.2016-WJZD-10)。

摘　　要：目的:探讨紫甘薯花色苷(purple sweet potato anthocyanin,PSPA)是否通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。方法:选用乳腺癌MDA-MB-231细胞,将其分为对照组,200、400和800μg/ml PSPA组,pcDNA组、pcDNA-circ_0003998组、si-NC组、si-circ_0003998组、si-circ_0003998+anti-miR-145组、PSPA+pcDNA组、PSPA+pcDNA-circ_0003998组和PSPA+anti-miR-145组。用qPCR法检测细胞中circ_0003998和miR-145的表达,CCK-8法、Transwell小室法分别检测转染前后细胞的增殖、迁移和侵袭能力,WB法检测细胞中Ki-67、MMP-2和MMP-9蛋白的表达。用双荧光素酶报告基因实验验证circ_0003998与miR-145的靶向关系。结果:与对照组比较,各剂量PSPA组MDA-MB-231细胞的增殖抑制率、miR-145表达水平均显著升高(均P<0.01),Ki-67、MMP-2、MMP-9蛋白和circ_0003998的表达水平、细胞迁移和侵袭细胞数均显著降低(均P<0.01),并呈现浓度依赖性。circ_0003998可以靶向负调控miR-145的表达。敲减circ_0003998后,MDA-MB-231细胞的增殖抑制率、miR-145表达水平显著升高,Ki-67、MMP-2和MMP-9蛋白表达水平、细胞迁移和侵袭细胞数均显著减少(均P<0.01)。共转染si-circ_0003998和anti-miR-145则可逆转敲减circ_0003998表达对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用,过表达circ_0003998或抑制miR-145表达可逆转PSPA对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用。结论:PSPA通过circ_0003998/miR-145轴抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。Objective:To investigate whether purple sweet potato anthocyanin(PSPA)regulates the proliferation,migration and invasion of breast cancer MDA-MB-231 cells through the circ_0003998/miRNA-145 axis.Methods:Breast cancer MDA-MB-231 cells were divided into control group,PSPA groups(200,400,800μg/ml PSPA),pcDNA group,pcDNA-circ_0003998 group,si-NC group,si-circ_0003998 group,si-circ_0003998+anti-miR-145 group,PSPA+pcDNA group,PSPA+pcDNA-circ_0003998 group and PSPA+anti-miR-145 group.The expressions of circ_0003998 and miR-145 in MDA-MB-231 cells were detected by qPCR method.The cell proliferation,migration and invasion abilities were measured by CCK-8 method and Transwell chamber method,respectively.WB was used to detect the protein expressions of Ki-67,MMP-2 and MMP-9 in cells.Dual luciferase reporter gene assay was used to analyze the targeting relationship between circ_0003998 and miR-145.Results:Compared with the control group,the proliferation inhibition rate and miR-145 expression level in MDA-MB-231 cells of various PSPA groups increased significantly,while the expression of circ_0003998 and protein expression levels of Ki-67,MMP-2,MMP-9,as well as the number of migrated and invaded cells were significantly reduced(all P<0.01),all of which were in a concentration-dependent manner.circ_0003998 could target and negatively regulate the expression of miR-145.After inhibiting circ_0003998,the proliferation inhibition rate and the expression level of miR-145 in MDA-MB-231 cells were significantly increased,while the protein expression levels of Ki-67,MMP-2 and MMP-9,and the number of migrated and invaded cells were significantly reduced(all P<0.01).After co-transfection of si-circ_0003998 and anti-miR-145,the suppression effect of circ_0003998 inhibition on the proliferation,migration and invasion of MDA-MB-231 cells were reversed.circ_0003998 overexpression or miR-145 inhibition could reverse the inhibitory effects of PSPA on the proliferation,migration and invasion of MDA-MB-231 cells.Conclusion:PSPA inhibites the

关 键 词：紫甘薯花色苷 circ_0003998 MIR-145 乳腺癌 MDA-MB-231细胞 增殖 迁移 侵袭 

分 类 号：R737.9[医药卫生—肿瘤] R730.2[医药卫生—临床医学]