title: MicroRNA-148a inhibits breast cancer migration and invasion by directly targeting WNT-1.
abstract: Wnt/β-catenin signaling pathway influences embryonic development, cell polarity and adhesion, apoptosis and tumorigenesis. MicroRNAs (miRNAs) function as important regulators of the tumorigenesis and metastasis. In the present study, we aimed to find novel targets and mechanisms of microRNA-148a (miR-148a) in regulating the migration and invasion of breast cancer cells. In the present study, miR-148a was found downregulated in human breast cancer tissues and cell lines. The ectopic miR-148a expression inhibited the migration and invasion of MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we demonstrated that WNT-1, one of the ligands of Wnt/β-catenin signaling pathway, was a direct target of miR-148a. The overexpression of miR-148a reduced the mRNA and protein expression levels of WNT-1, also decreased the expression levels of the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteinase-7 (MMP-7) and T-cell factor-4 (TCF-4) in MCF-7 and MDA-MB-231 cells. In addition, the data showed that the expression of WNT-1 was significantly higher in human breast cancer tissues compared with the adjacent normal tissues and the expression of miR-148a was negatively correlated with the WNT-1 expression in human breast cancer tissues. Taken together, our results suggest that miR-148a can suppress the migration and invasion of breast cancer cells by targeting WNT-1 and inhibiting Wnt/β-catenin signaling pathway and this will provide new insights into the molecular mechanisms of breast cancer metastasis.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Hui-Zhe
authors.initials: HZ
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Zhao-Jin
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Shu
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Long-Yang
authors.initials: LY
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Da-Di
authors.initials: DD
authors.lastname: Zheng
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wei
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D060449:Wnt Signaling Pathway / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051155:Wnt1 Protein; D051176:beta Catenin