title: MicroRNA-409-3p regulates cell invasion and metastasis by targeting ZEB1 in breast cancer.
abstract: MicroRNA-409-3p (miR-409-3p) is an miRNA expressed by embryonic stem cells, and our previous study demonstrated depressed miR-409-3p expression in human breast cancer (BC) cell lines; however, its role and function in BC metastasis are still unknown. The purpose of this study was to examine the expression levels of miR-409-3p in human BC and its role in the metastasis of BC. We analyzed the status of miR-409-3p expression in BC tissues by quantitative real-time polymerase chain reaction (PCR) and its relationship to the clinicopathologic features of patients with BC. To study the role of miR-409-3p in BC metastasis, the invasion ability of BC cells was detected by transwell invasion assays and wound healing assays. WST-1 assays and colony formation assays were used to investigate cell proliferation. Luciferase reporter assays were used to verify that miR-409-3p targeted zinc-finger E-box-binding homeobox 1 (ZEB1). Western blot analyses and transwell assays were carried out to assess ZEB1 expression and its role in BC cell metastasis. The expression of miR-409-3p was lower in tumor tissues than in noncancerous breast tissues. We verified that miR-409-3p levels were downregulated and significantly correlated with poor outcomes in patients with BC. Overexpression of miR-409-3p inhibited cellular proliferation and suppressed cellular migration and invasion in vitro and in vivo. Dual-luciferase reporter assays showed that miR-409-3p binds the 3'-untranslated region (3'-UTR) of ZEB1, suggesting that ZEB1 is a direct target of miR-409-3p. Western blot analysis confirmed that overexpression of miR-409-3p reduced ZEB1 protein levels. These data demonstrate that miR-409-3p plays an important role in regulating the metastasis of BC, which is involved in the post-transcriptional repression of ZEB1. Our results indicate that miR-409-3p can regulate the invasion and metastasis process of BC by targeting ZEB1 and may serve as a new prognostic marker and therapeutic target for treating BC metastasis. © 2016 IUBMB Life, 68(5):394-402, 2016.
authors.affiliation: Breast Cancer Key Laboratory of Dalian, Department of Breast Disease and Reconstruction Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Breast Cancer Key Laboratory of Dalian, Department of Breast Disease and Reconstruction Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Breast Cancer Key Laboratory of Dalian, Department of Breast Disease and Reconstruction Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Breast Cancer Key Laboratory of Dalian, Department of Breast Disease and Reconstruction Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Qiaozhen
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
authors.affiliation: Breast Cancer Key Laboratory of Dalian, Department of Breast Disease and Reconstruction Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Tian
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034622:RNA Interference; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C572367:MIRN409 microRNA, human; D035683:MicroRNAs; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: ZEB1; breast cancer; invasion; metastasis; miR-409-3p