中国肿瘤生物治疗杂志2017，Vol.24Issue(7)：733-741,9.DOI:10.3872/j.issn.1007-385x.2017.07.007
miR-133通过Notch1信号通路调控BCAR4对乳腺癌迁移和侵袭的影响
miR-133 manages effect of BCAR4 on migration and invasion of the breast cancer cells through Notch1 signaling pathway
摘要
Abstract
Objective:To explore microRNA-133 (miR-133) controling effect of breast cancer anti-estrogen resistance 4 (BCAR4)gene on migration and invasion of the breast cancer cells as well as its mechanism.Methods:Breast cancer and corresponding paracancerous tissues from the 80 patients with breast caner who were hospitalized in Tumor Hospital affiliated to Zhengzhou University for surgical resection treatment during January to December 2016 were collected.Expressions of BCAR4 and miR-133 in the breast cancer and paracancerous tissues were detected by RT-PCR.A association between BCAR4 and miR-133 was tested by a dual-luciferase assay.Scratch and Transwell assays were respectively used to examine migration and invasion of the breast cancer MCF-7 cell after silencing BCAR4 or silencing BCAR4 and miR-133.Expressions of the Notchl signaling pathway-related proteins were detected by Western blotting assay.A subcutaneous xenograft tumor experiment in nude mice was used to examine effect of silencing BCAR4 on ability of forming tumor of the MCF-7 cell in vivo.Relationships between expression of BCAR4 and clinicopathological parameters as well as survival rate of the patients with breast cancer were analyzed by biostatistics.Results:Expression of BCAR4 in the breast cancer tissue was significantly higher than that in the para-cancer tissue(P＜0.05).Result of dual-luciferase assay shown that BCAR4 could manage expression of miR-133.Silencing expression of BCAR4 could inhibit migration and invasion of the MCF-7 cell.Migration rate and transmembrane cell number of the MCF-7 cell in which expressions of miR-133 and BCAR4 were silenced were obviously higher than those of the MCF-7 cell in which only expression of BCAR4 was silenced [migration rate:(92.31 ±8.64)％ vs (52.61 ±5.12)％,P＜0.05;transmembrane cell number:(171.38± 12.61) vs (28.54±3.29),P＜0.01].Restrain of miR-133 could reverse inhibition of BCAR4 to migration and invasion of the MCF-7 cell.Volumes and wights of the xenograft tumors of the nude mice in which BCAR4 was silenced were significantly decreased.Expressions of Notchl signaling pathway-related proteins of the MCF-7 cell in which BCAR4 was silenced were remarkably down-regulated.Expression of BCAR4 was significantly related to pathological staging and lymph node metastasis of the patients with breast cancer.Survival rate of the patients with high expression of BCAR4 were lower than that of the patients with low expression of BCAR4.Conclusion:Migration and invasion of the breast cancer MCF-7 cell might be doubly managed by BCAR4 and miR-133.miR-133 could targetly regulate effect of BCAR4 on migration and invasion of the breast cancer cell through the Notchl signaling pathway,which might give some clues for the molecular targeting therapy of breast cancer and the research on drug resistance mechanism of breast cancer.关键词
乳腺癌抗雌激素耐药基因4/乳腺癌/微小核糖核酸-133/迁移/侵袭Key words
breast cancer anti-estrogen resistance 4 (BCAR4) gene/breast cancer/micro ribonucleic acid-133 (miR-133)/migration/invasion分类
医药卫生引用本文复制引用
张建波,宋魏,王媛媛,刘明阁,孙淼淼..miR-133通过Notch1信号通路调控BCAR4对乳腺癌迁移和侵袭的影响[J].中国肿瘤生物治疗杂志,2017,24(7):733-741,9.基金项目
河南省基础与前沿技术研究计划基金资助项目(No.102300410038).Project supported by the Basic and Frontier Technology Research Program Foundation of Henan Province (No.102300410038) （No.102300410038）
