title: MicroRNA-494 inhibits breast cancer progression by directly targeting PAK1.
abstract: MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro. Moreover, ectopic expression of miR-494 suppresses neoplasm initiation as well as pulmonary metastasis in vivo. Further studies have identified PAK1, as a direct target gene of miR-494, contributes to the functions of miR-494. Remarkably, the expression of PAK1 is inversely correlated with the level of miR-494 in human breast cancer samples. Furthermore, re-expression of PAK1 partially reverses miR-494-mediated proliferative and clonogenic inhibition as well as migration and invasion suppression in breast cancer cells. Taken together, these findings highlight an important role for miR-494 in the regulation of progression and metastatic potential of breast cancer and suggest a potential application of miR-494 in breast cancer treatment.
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Meng-Na
authors.initials: MN
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Tong-Ji Hospital Affiliated to Tong-Ji University School of Medicine, Shanghai, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Yu
authors.affiliation: Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Ci-Xiang
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Chen-Long
authors.initials: CL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Yin
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Gong
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: He
authors.affiliation: Department of General Surgery, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: He
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.|Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology and Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C547168:MIRN494 microRNA, human; D035683:MicroRNAs; C515903:PAK1 protein, human; D054462:p21-Activated Kinases