MiR-507 inhibits the migration and invasion of human breast-cancer cells through Flt-1 suppression

被引:28
作者
Jia, Liyan [1 ]
Liu, Wei [1 ]
Cao, Bo [1 ]
Li, Hongli [2 ]
Yin, Chonggao [3 ]
机构
[1] Weifang Med Univ, Affiliated Hosp, Weifang 261053, Peoples R China
[2] Weifang Med Univ, Med Res Ctr, Weifang 261053, Peoples R China
[3] Weifang Med Univ, Coll Nursing, Weifang 261053, Peoples R China
关键词
miR-507; Flt-1; molecular mechanism; invasion; PlGF-1; EPIGENETIC MECHANISMS; ACTIN POLYMERIZATION; METASTASIS; MICRORNAS; TARGET; PHOSPHORYLATION; MOTILITY; GROWTH; GLIOMA; EGF;
D O I
10.18632/oncotarget.9163
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase-1 (VEGFR-1/Flt-1) is a tyrosine kinase receptor that binds placental growth factor (PlGF). Flt-1 is also highly expressed in breast-cancer tissues and breast-cancer cell lines. However, the molecular mechanism by which Flt-1 promotes breast-cancer invasion and metastasis by binding to PlGF-1 is unclear. In this study, we discovered that PlGF-1 and Flt-1 played a key role in the migration and invasion of breast cancer. Flt-1 promoted the migration and chemotaxis of breast-cancer cells by binding to PlGF-1. In addition, Flt-1 was confirmed to be a direct target gene of miR-507. miR-507 up-regulation inhibited the invasion and metastasis of breast-cancer cells in vitro and in vivo. Flt-1 overexpression rescued the invasion partially caused by the ectopic expression of miR-507. miR-507 expression in breast-cancer tissues and cell lines was lower than that in adjacent non-neoplastic tissues and normal cells. Clinical analysis indicated that miR-507 was negatively correlated with tumor differentiation, lymphatic metastasis, and the expression of Flt-1 in breast cancer. Furthermore, we showed that miR-507 down-regulation was due to the hypermethylation of its promotor region. Our results indicated that miR-507 represented potential therapeutic targets in breast cancer by modulating Flt-1.
引用
收藏
页码:36743 / 36754
页数:12
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