miR-133通过Notch1信号通路调控BCAR4对乳腺癌迁移和侵袭的影响

发布时间：2018-05-06 09:54

本文选题：乳腺癌抗雌激素耐药基因 + 乳腺癌　；参考：《中国肿瘤生物治疗杂志》2017年07期

【摘要】：目的:探讨微小核糖核酸-133(mi R-133)调控乳腺癌雌激素耐受基因4(breast cancer anti-estrogen resistance 4,BCAR4)对乳腺癌细胞迁移和侵袭的影响及其机制。方法:采集2006年1至12月在郑州大学附属肿瘤医院接受手术切除治疗的80例乳腺癌患者的乳腺癌和相应癌旁组织。RT-PCR检测乳腺癌和癌旁组织BCAR4和mi R-133的表达;双荧光素酶检测BCAR4和mi R-133之间的关联;划痕实验和Transwell实验分别检测沉默BCAR4或沉默BCAR4和mi R-133后乳腺癌MCF-7细胞的迁移和侵袭能力;Western blotting检测Notch1信号通路相关蛋白的表达;裸鼠皮下成瘤实验检测沉默BCAR4对MCF-7细胞成瘤能力的影响;生物统计学分析BCAR4表达和乳腺癌患者临床病理参数及生存率的关系。结果:乳腺癌组织中BCAR4表达显著高于癌旁组织(P0.05);双荧光素酶实验显示BCAR4可以调控mi R-133的表达;沉默BCAR4表达可以抑制乳腺癌MCF-7细胞的迁移和侵袭;沉默mi R-133和BCAR4表达的MCF-7细胞的迁移率和穿膜细胞数显著高于仅沉默BCAR4表达的MCF-7细胞[迁移率(92.31±8.64)%vs(52.61±5.12)%,P0.05;穿膜细胞数:(171.38±12.61)vs(28.54±3.29),P0.01],抑制mi R-133可以逆转BCAR4抑制乳腺癌MCF-7细胞迁移、侵袭能力;沉默BCAR4组裸鼠成瘤的体积和质量都显著减小;沉默BCAR4的MCF-7细胞的Notch1通路相关蛋白表达水平明显下调;BCAR4表达与乳腺癌的病理分期及淋巴结转移显著相关,BCAR4高表达患者生存率较BCAR4低表达患者低。结论:乳腺癌MCF-7细胞的侵袭和迁移受到BCAR4和mi R-133的双重调控,mi R-133可能通过Notch1信号通路调节BCAR4对乳腺癌细胞迁移和侵袭的影响,可为乳腺癌分子靶向治疗及乳腺癌耐药机制的研究提供思路。
[Abstract]:Aim: to investigate the effects of small ribonucleic acid (RNC-133mR-133) on the migration and invasion of breast cancer cells regulated by the estrogen tolerance gene 4(breast cancer anti-estrogen resistance 4 (BCAR4) and its mechanism. Methods: the expressions of BCAR4 and miR-133 in breast cancer and adjacent tissues were detected by RT-PCR in 80 patients with breast cancer treated by surgical excision from January to December 2006 in the affiliated Cancer Hospital of Zhengzhou University. The relationship between BCAR4 and miR-133 was detected by double luciferase assay, the migration and invasion ability of breast cancer MCF-7 cells after silencing BCAR4 or silencing BCAR4 and miR-133 was detected by scratch test and Transwell assay respectively. Western blotting was used to detect the expression of Notch1 signal pathway related protein. The effect of silencing BCAR4 on the tumorigenesis of MCF-7 cells was detected by subcutaneous tumorigenesis assay in nude mice, and the relationship between BCAR4 expression and clinicopathological parameters and survival rate of breast cancer patients was analyzed by biostatistics. Results: the expression of BCAR4 in breast cancer tissues was significantly higher than that in adjacent tissues (P 0.05), double luciferase assay showed that BCAR4 could regulate the expression of miR-133, and silencing BCAR4 expression could inhibit the migration and invasion of breast cancer MCF-7 cells. The migration rate and the number of perforating cells of MCF-7 cells silencing the expression of miR-133 and BCAR4 were significantly higher than those of MCF-7 cells only silencing the expression of BCAR4 [migration rate was 92.31 卤8.64)%vs(52.61 卤5.12], and the number of transmembrane cells was 171.38 卤12.61)vs(28.54 卤3.29P0.01, and the inhibition of MIR-133 could reverse the ability of BCAR4 to inhibit the migration and invasion of MCF-7 cells of breast cancer. In silencing BCAR4 group, the tumor size and mass of nude mice decreased significantly. The expression level of Notch1 pathway related protein in MCF-7 cells silenced by BCAR4 was significantly lower than that in patients with low expression of BCAR4, and the expression of BCAR4 was significantly correlated with the pathological stage and lymph node metastasis of breast cancer. The survival rate of patients with high expression of BCAR4 was significantly lower than that of patients with low expression of BCAR4. Conclusion: the invasion and migration of breast cancer MCF-7 cells are regulated by BCAR4 and miR-133, which may regulate the effect of BCAR4 on the migration and invasion of breast cancer cells through Notch1 signaling pathway. It can provide ideas for molecular targeted therapy of breast cancer and the mechanism of drug resistance in breast cancer.
【作者单位】：郑州大学附属肿瘤医院病理科;
【基金】：河南省基础与前沿技术研究计划基金资助项目(No.102300410038)~~
【分类号】：R737.9

【参考文献】