title: MiR-507 inhibits the migration and invasion of human breastcancer cells through Flt-1 suppression.
abstract: 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.
authors.affiliation: Affiliated Hospital, Weifang Medical University, Weifang, 261053, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Jia
authors.affiliation: Affiliated Hospital, Weifang Medical University, Weifang, 261053, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Affiliated Hospital, Weifang Medical University, Weifang, 261053, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.affiliation: Medicine Research Center, Weifang Medical University, Weifang, 261053, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Nursing, Weifang Medical University, Weifang, 261053, China.
authors.forename: Chonggao
authors.initials: C
authors.lastname: Yin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002633:Chemotaxis / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D000072483:Placenta Growth Factor / Q000494:pharmacology; D034622:RNA Interference; D014183:Transplantation, Heterologous; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C000625712:MIRN507 microRNA, human; D035683:MicroRNAs; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Flt-1; PlGF-1; invasion; miR-507; molecular mechanism