Repression of Smad4 by miR-205 moderates TGF-β-induced epithelial-mesenchymal transition in A549 cell lines

被引：54

作者：

Zeng, Yuanyuan ^{[1
,4
]}

Zhu, Jianjie ^{[1
]}

Shen, Dan ^{[1
]}

Qin, Hualong ^{[2
]}

Lei, Zhe ^{[5
]}

Li, Wei ^{[3
]}

Huang, Jian-An ^{[1
,4
]}

Liu, Zeyi ^{[1
,4
]}

机构：

[1] Soochow Univ, Affiliated Hosp 1, Dept Resp Med, Suzhou 215123, Jiangsu, Peoples R China

[2] Soochow Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Suzhou 215123, Jiangsu, Peoples R China

[3] Soochow Univ, Affiliated Hosp 1, Dept Oncol, Suzhou 215123, Jiangsu, Peoples R China

[4] Soochow Univ, Inst Resp Dis, Suzhou 215123, Jiangsu, Peoples R China

[5] Suzhou Key Lab Mol Canc Genet, Suzhou, Peoples R China

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2016年 / 49卷 / 02期

基金：

中国国家自然科学基金;

关键词：

non-smallcell lung cancer; miR-205; TGF-beta/Smad signaling pathway; Smad4; epithelial-mesenchymal transition; LUNG-CANCER; EXPRESSION; TUMOR; MICRORNAS; HSA-MIR-205; METASTASIS; MECHANISMS; SURVIVAL; RECEPTOR; GENE;

D O I：

10.3892/ijo.2016.3547

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The TGF-beta Smad signaling pathway plays important roles in cancer cell proliferation, apoptosis, differentiation, angiogenesis and epithelial-mesenchymal transition (EMT), which is the key event in the early stages of cancer metastasis and enhances the capability of cell migration and invasion. Smad4 acts as the only Co-Smad of TGF/Smad signaling pathway and plays the key role in TGF-beta-mediated EMT. Nevertheless, the mRNA regulation mechanisms of Smad4 in human non-small cell lung cancer (NSCLC) remains largely unclear. Computational algorithms predicted that the 3'-UTR of Smad4 is a target of miR-205. Here, we validated that miR-205 could directly bind to 3'-UTR of Smad4 by luciferase assays. Moreover, we investigated the functional roles of miR-205 and its molecular link to Smad4 in lung cancer cells. In this study, we confirmed that overexpression of miR-205 suppressed the expression of Smad4, in turn, weakened the TGF-beta/Smad signaling pathway and inhibited TGF-beta/Smad4-induced EMT, invasion and migration ultimately. Furthermore, this study shows that miR-205 can serve as a promising therapeutic target of highly aggressive NSCLC.

引用

页码：700 / 708

页数：9