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MicroRNA‐409‐3p regulates cell invasion and metastasis by targeting ZEB1 in breast cancer
Author(s) -
Ma Zhenhai,
Li Yang,
Xu Jingchao,
Ren Qiaozhen,
Yao Jihong,
Tian Xiaofeng
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1494
Subject(s) - microrna , metastasis , cancer research , biology , cell migration , cell growth , western blot , zinc finger , reporter gene , cancer , luciferase , cell , cell culture , microbiology and biotechnology , gene expression , transfection , gene , transcription factor , genetics
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