miR-190 suppresses breast cancer metastasis by regulation of TGF-β-induced epithelial-mesenchymal transition

• Published in: Molecular cancer Vol. 17; no. 1; p. 70
• Main Authors: Yu, Yue, Luo, Wei, Yang, Zheng-Jun, Chi, Jiang-Rui, Li, Yun-Rui, Ding, Yu, Ge, Jie, Wang, Xin, Cao, Xu-Chen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06-03-2018; BioMed Central; BMC
• Subjects: 3' Untranslated Regions; Analysis; Animals; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Care and treatment; Cell Line, Tumor; Diagnosis; Disease Models, Animal; Down-Regulation; Embryonic development; Epithelial to mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Metastasis; Mice; MicroRNA; MicroRNAs - genetics; miR-190; Models, Biological; Neoplasm Metastasis; Neoplasm Staging; Nucleotide Motifs; Promoter Regions, Genetic; RNA Interference; Signal Transduction; SMAD2; Smad2 Protein - genetics; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; Transforming growth factor-β; Transforming growth factors; Xenograft Model Antitumor Assays; ZEB1; Epithelial to mesenchymal transition; SMAD2; Breast cancer; ZEB1; miR-190; Transforming growth factor-β
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-018-0818-9

Breast cancer is the most common cancer among women worldwide and metastasis is the leading cause of death among patients with breast cancer. The transforming growth factor-β (TGF-β) pathway plays critical roles during breast cancer epithelial-mesenchymal transition (EMT) and metastasis. SMAD2, a positive regulator of TGF-β signaling, promotes breast cancer metastasis through induction of EMT.
The expression of miR-190 and SMAD2 in breast cancer tissues, adjacent normal breast tissues and cell lines were determined by RT-qPCR. The protein expression levels and localization were analyzed by western blotting and immunofluorescence. ChIP and dual-luciferase report assays were used to validate the regulation of ZEB1-miR-190-SMAD2 axis. The effect of miR-190 on breast cancer progression was investigated both in vitro and in vivo.
miR-190 down-regulation is required for TGF-β-induced EMT. miR-190 suppresses breast cancer metastasis both in vitro and in vivo by targeting SMAD2. miR-190 expression is down-regulated and inversely correlates with SMAD2 in breast cancer samples, and its expression level was associated with outcome in patients with breast cancer. Furthermore, miR-190 is transcriptionally regulated by ZEB1.
Our data uncover the ZEB1-miR-190-SMAD2 axis and provide a mechanism to explain the TGF-β network in breast cancer metastasis.