靶向miR-592/PIK3CA的lncRNA-XIST对乳腺癌细胞裸鼠的作用机制探究  

Mechanism of lncRNA-XIST Targeting miR-592/PIK3CA on Nude Mice with Breast Cancer Cells

作　　者：金聪慧[1] 苗波波 李桃 倪静怡[1] 张珣磊 张葆春 高湘湘[1] JIN Cong-hui;MIAO Bo-bo;LI Tao;NI Jing-yi;ZHANG Xun-lei;ZHANG Bao-chun;GAO Xiang-xiang(Department ofMedical Oncology,Tumor Hospital Affiliated to Nantong University,Nantong,Jiangsu,226001,China;Department of Pathology,Affiliated Hospital of Nantong University,Nantong,Jiangsu,226000,China)

机构地区：[1]南通大学附属肿瘤医院肿瘤内科,江苏南通226001 [2]南通大学附属医院病理科,江苏南通226000

出　　处：《现代生物医学进展》2024年第6期1038-1043,共6页Progress in Modern Biomedicine

基　　金：江苏省卫健委指导性项目(Z2022036);江苏省南通市科技计划指导性项目(JCZ21109);江苏省南通市卫建委面上课题B(MB2021043)。

摘　　要：目的:探讨靶向miR-592/PIK3CA的lncRNA-XIST对乳腺癌细胞裸鼠的作用机制。方法:选择2021年1月至2022年我院收集的20例乳腺癌组织及癌旁组织,对比lncRNA XIST、miR-592及PIK3CA的表达水平。培养MCF-10A、MCF-7、BT-549、MDA-MB-468、HSS578T细胞,对比不同乳腺癌细胞中lncRNA XIST、mi R-592及PIK3CA的表达。建立MCF-7裸鼠移植瘤模型建立,将其分为对照组、si-NC组、si-XIST组、pcDNA-NC组、pcDNA-XIST组,对比不同组荷瘤裸鼠生存情况及各组肿瘤体积、抑瘤率。使用Western blot法检测MMP-2、MMP-9、Bax蛋白表达,之后行双荧光素酶报告基因实验。结果:乳腺癌组织中的lncRNA XIST表达水平明显较癌旁组织低,miR-592、PIK3CA表达水平明显较癌旁组织高(P<0.05)。与MCF-10A正常乳腺癌细胞相比,MCF-7乳腺癌细胞中lncRNA XIST表达最低,miR-592、PIK3CA表达最高,选择MCF-7乳腺癌细胞作为研究对象行后续研究。对照组、si-NC组、pcDNA-NC组的肿瘤体积、肿瘤重量对比无统计学意义,si-NC组、pcDNA-NC组的抑瘤率对比无统计学意义(P>0.05);si-XIST组的肿瘤体积、肿瘤重量明显增加(P<0.05),抑瘤率为-40.04±5.24%,pcDNA-XIST组肿瘤体积、肿瘤重量明显降低(P<0.05),抑瘤率为54.29±7.89%。对照组、si-NC组、pcDNA-NC组的MMP-2、MMP-9、Bax对比无统计学意义(P>0.05);与对照组、si-NC组、pcDNA-NC组相比,si-XIST组的MMP-2、MMP-9明显升高,Bax明显降低,pcDNA-XIST组的MMP-2、MMP-9明显降低,Bax明显升高(P<0.05)。与mimic NC相比,mi R-592 mimic组中XIST-WT、PIK3CA-WT细胞中荧光活性明显降低(P<0.05),两组XIST-MUT、PIK3CA-MUT细胞中荧光活性对比无统计学意义(P>0.05)。结论:过表达XIST可能通过海绵化miR-592来调控PIK3CA表达水平,降低MMP-2、MMP-9水平,提高Bax水平,进而抑制MCF-7裸鼠皮下移植瘤的生长。Objective:To investigate the mechanism of action of lncRNA-XIST targeting miR-592/PIK3CA on nude mice with breast cancer cells.Methods:The expression levels of lncRNA XIST,miR-592 and PIK3CA were compared in 20 breast cancer tissues and adjacent tissues collected in our hospital from January 2021 to 2022.MCF-10A,MCF-7,BT-549,MDA-MB-468,HSS578T cells were cultured,and the expressions of lncRNA XIST,miR-592 and PIK3CA in different breast cancer cells were compared.The transplanted tumor model of MCF-7 nude mice was established,and the mice were divided into control group,si-NC group,si-XIST group,pcDNA-NC group and pcDNA-XIST group,and the survival status,tumor volume and tumor inhibition rate of each group were compared.Western blot was used to detect the expression of MMP-2,MMP-9 and Bax proteins,and then double luciferase reporter gene assay was performed.Results:In breast cancer tissues,the expression level of lncRNA XIST was lower,and the expression levels of miR-592 and PIK3CA were higher(P<0.05).Compared with MCF-10A normal breast cancer cells,the expression of lncRNA XIST in MCF-7 breast cancer cells was the lowest,and the expression of miR-592 and PIK3CA was the highest.MCF-7 breast cancer cells were selected as the research objects for follow-up studies.There was no statistical significance in tumor volume and weight in control group,si-NC group and pcDNA-NC group,and no significance in tumor inhibition rate between si-NC group and pcDNA-NC group(P>0.05).The tumor volume and weight of the si-XIST group were increased(P<0.05),and the tumor inhibitory rate was-40.04±5.24%;the tumor volume and weight of the pcDNA-XIST group were decreased(P<0.05),and the tumor inhibitory rate was 54.29±7.89%.There was no significance in MMP-2,MMP-9 and Bax of control group,si-NC group and pcDNA-NC group(P>0.05).Compared with control group,si-NC group and pcDNA-NC group,MMP-2 and MMP-9 in si-XIST group were significantly increased,and Bax was significantly decreased,MMP-2 and MMP-9 were significantly decreased,and Bax was i

关 键 词：miR-592/PIK3CA lncRNA-XIST 乳腺癌 裸鼠 作用机制 

分 类 号：R-33[医药卫生] R737.9