title: MicroRNA-320a inhibits breast cancer metastasis by targeting metadherin.
abstract: Dysregulated microRNAs play important pathological roles in carcinogenesis that are yet to be fully elucidated. This study was performed to investigate the biological functions of microRNA-320a (miR-320a) in breast cancer and the underlying mechanisms. Function analyses for cell proliferation, cell cycle, and cell invasion/migration, were conducted after miR-320a silencing and overexpression. The specific target genes of miR-320a were predicted by TargetScan algorithm and then determined by dual luciferase reporter assay and rescue experiment. The relationship between miR-320a and its target genes was explored in human breast cancer tissues. We found that miR-320a overexpression could inhibit breast cancer invasion and migration abilities in vitro, while miR-320a silencing could enhance that. In addition, miR-320a could suppress activity of 3'-untranslated region luciferase of metadherin (MTDH), a potent oncogene. The rescue experiment revealed that MTDH was a functional target of miR-320a. Moreover, we found that MTDH was negatively correlated with miR-320a expression, and it was related to clinical outcomes of breast cancer. Further xenograft experiment also showed that miR-320a could inhibit breast cancer metastasis in vivo. Our findings clearly demonstrate that miR-320a suppresses breast cancer metastasis by directly inhibiting MTDH expression. The present study provides a new insight into anti-oncogenic roles of miR-320a and suggests that miR-320a/MTDH pathway is a putative therapeutic target in breast cancer.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Ji-Gang
authors.initials: JG
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, People's Hospital, Linzi District, Zibo 255400, China.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Di
authors.initials: D
authors.lastname: Ding
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ke-Han
authors.initials: KH
authors.lastname: Ren
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Dan-Mei
authors.initials: DM
authors.lastname: Zhou
authors.affiliation: Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zou
authors.affiliation: Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Jin
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.|Department of Pathology, The Fifth People's Hospital, Fudan University, Shanghai 200240, China.
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016601:RNA-Binding Proteins; D014162:Transfection
chemical_list: D015815:Cell Adhesion Molecules; C572916:MIRN320 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins
keywords: MTDH; breast cancer; metastasis; miR-320a