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Downregulation of miR‐3127‐5p promotes epithelial‐mesenchymal transition via FZD4 regulation of Wnt/β‐catenin signaling in non‐small‐cell lung cancer
Author(s) -
Yang Yang,
Sun Yifeng,
Wu Yun,
Tang Dongfang,
Ding Xi,
Xu Wen,
Su Bo,
Gao Wen
Publication year - 2018
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22805
Subject(s) - downregulation and upregulation , wnt signaling pathway , biology , epithelial–mesenchymal transition , cancer research , microrna , metastasis , cancer , signal transduction , microbiology and biotechnology , gene , genetics
MiR‐3127‐5p has been implicated as a tumor‐suppressive microRNA (miRNA) in non‐small‐cell lung cancer (NSCLC) and its expression was associated with tumor recurrence and poor prognosis. The aim of this study was to determine whether miR‐3127‐5p regulates epithelial‐mesenchymal transition (EMT) in NSCLC, and to investigate the underlying mechanisms. Using qRT‐PCR, we examined the expression levels of miR‐3127‐5p in a cohort of primary NSCLC specimens with and without distant metastasis. We further performed a series of in vitro and in vivo experiments to investigate the effects and underlying mechanism of miR‐3127‐5p on EMT, cell migration, invasion, and adhesion in NSCLC. We found that metastatic NSCLC tissues showed markedly downregulated miR‐3127‐5p expression. Transforming growth factor‐β1 (TGF‐β1) treatment induced EMT in A549 and H1299 cells, and downregulation of miR‐3127‐5p could result in the similar effect. Mechanically, we demonstrated that frizzled‐4 (FZD4) is a target gene and miR‐3127‐5p exerts its effects by regulating the Wnt/β‐catenin signaling. In addition, the expression levels of FZD4 and miR‐3127‐5p were also negatively associated in both clinical and xenografted tumors. Overall, these findings suggest that downregulation of miR‐3127‐5p promotes EMT through activating the Wnt/FZD4/β‐catenin signaling pathway and may represent a therapeutic target for NSCLC metastasis.