TRIM52-AS1靶向微小RNA-378a-3p对乳腺癌细胞迁移侵袭和NF-Κb信号通路的影响
Effects of TRIM52-AS1 on migration,invasion and NF-κB signaling pathway of breast cancer cells by targeting microRNA-378a-3p
乔峰 1沙亚滨 2吴波 1李琳 1姜晓玲3
作者信息
- 1. 250031 济南 解放军第九六〇医院普外科
- 2. 250011 济南市第一人民医院血液透析科
- 3. 271099 泰安市中心医院病理科
- 折叠
摘要
目的 阐述TRIM52 反义RNA 1(TRIM52-AS1)靶向微小RNA-378a-3p(miR-378a-3p)在乳腺癌细胞增殖、迁移和侵袭中的生物学作用.方法 qPCR检测乳腺癌细胞中TRIM52-AS1 的表达情况,双荧光素酶报告基因实验验证TRIM52-AS1 和miR-378a-3p的靶向关系,培养BT474 细胞并进行分组:siRNA-NC组(阴性对照)、siRNA-TRIM52-AS1 组(沉默TRIM52-AS1 表达)和siRNA-TRIM52-AS1+miR-378a-3p inhibitor组(同时沉默TRIM52-AS1 和miR-378a-3p表达).噻唑蓝比色(MTT)法、划痕实验和Transwell实验检测BT474 细胞的增殖、迁移和侵袭情况,Western blot检测磷酸化核因子κB(NF-κB)p65、核因子κB抑制蛋白(IKBα)的磷酸化水平.结果 TRIM52-AS1 在乳腺癌细胞中高表达(P＜0.05).与siRNA-NC组比较,siRNA-TRIM52-AS1 组细胞的增殖、迁移和侵袭能力减弱及 p-p65 水平降低和 p-IKBα水平升高(P＜0.05).miR-378a-3p是TRIM52-AS1 的靶基因且受TRIM52-AS1 的负调控.siRNA-TRIM52-AS1+miR-378a-3p inhibitor组较siRNA-TRIM52-AS1 组细胞的增殖、迁移和侵袭能力增强,且 p-IKBα水平降低及 p-p65 水平升高(P＜0.01).结论 TRIM52-AS1 通过靶向miR-378a-3p促进乳腺癌细胞的迁移和侵袭,调控NF-κB信号通路活性.TRIM52-AS1 作为癌症驱动因子,可能成为乳腺癌的潜在治疗靶点.
Abstract
Objective To identify the role of TRIM52 antisense RNA 1(TRIM52-AS1)on proliferation,migration and invasion of breast cancer cells through targeting microRNA-378a-3p(miR-378a-3p).Methods Expression levels of TRIM52-AS1 and miR-378a-3p in breast cancer cells were detected by qPCR assay.BT474 cells were allocated into siRNA-NC group,siRNA-TRIM52-AS1 group(TRIM52-AS1 silencing)and siRNA-TRIM52-AS1+miR-378a-3p inhibitor group(TRIM52-AS1 and miR-378a-3p silencing).The proliferation,migration and invasion abilities of BT474 cells were accessed by MTT,scratch and Transwell assays.Dual luciferase assay was used for analysis of the relationship between TRIM52-AS1 and miR-378a-3p.Western blot was used to detect the phosphorylation levels of nuclear factor kappa B(NF-κB)p65 and inhibitory protein IkB alpha(IKB-α).Results TRIM52-AS1 was over-regulated in breast cancer cells(P＜0.05).Compared with the siRNA-NC group,the siRNA-TTRIM52-AS1 group showed reduced proliferation,migration,and invasion abilities,as well as decreased p-p65 level and increased p-IKBα level(P＜0.05).As a target gene of TRIM52-AS1,miR-378a-3p was negatively regulated by TRIM52-AS1.The siRNA-TTRIM52-AS1+miR-378a-3p inhibitor group showed enhanced abilities of cells'proliferation,migration,and invasion compared to the siRNA-TTRIM52-AS1 group,with decreased p-IKBα level and increased p-p65 level(P＜0.01).Conclusion TRIM52-AS1 promotes migration and invasion of breast cancer cells by targeting miR-378a-3p and regulates NF-κB signaling pathway.TRIM52-AS1 acts as a cancer driver and may serve as a potential therapeutic target for breast cancer.
关键词
乳腺癌/TRIM52反义RNA/1/微小RNA-378a-3p/核因子κB信号通路/迁移/侵袭Key words
Breast cancer/TRIM52 antisense RNA 1/MicroRNA-378a-3p/Nuclear factor kappa B signaling pathway/Migration/Invasion引用本文复制引用
出版年
2024
NETL
NSTL
万方数据