title: MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression.
abstract: Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Kong
authors.forename: Gaopeng
authors.initials: G
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhang
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.forename: Wenyong
authors.initials: W
authors.lastname: Wu
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics; D010641:Phenotype; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D051416:Focal Adhesion Protein-Tyrosine Kinases; D035683:MicroRNAs; C549242:MIRN7-1 microRNA, human