title: MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway.
abstract: Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Huizhe
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Zhaojin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Longyang
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China.
authors.forename: Xingyue
authors.initials: X
authors.lastname: Zong
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning Province, People's Republic of China. weiminjiecmu@163.com.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000096:biosynthesis; D006801:Humans; D061986:MCF-7 Cells; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000096:biosynthesis; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C529739:Fzd8 protein, human; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D011956:Receptors, Cell Surface; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: Breast cancer; FZD-8; Invasion; MiR-100; Migration; Wnt/β-catenin signaling pathway