Smad3 regulates E-cadherin via miRNA-200 pathway

被引：91

作者：

Ahn, S-M ^{[2
,3
]}

Cha, J-Y ^{[2
]}

Kim, J. ^{[2
]}

Kim, D. ^{[2
]}

Trang, H. T. H. ^{[2
]}

Kim, Y-M ^{[2
]}

Cho, Y-H ^{[2
]}

Park, D. ^{[1
]}

Hong, S. ^{[2
]}

机构：

[1] Gachon Univ Gil Hosp, Dept Gastroenterol, Inchon, South Korea

[2] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Canc Cell Biol Lab, Dept Mol Med, Yeonsu 406840, Incheon, South Korea

[3] Gachon Univ Gil Hosp, Dept Translat Med, Inchon, South Korea

来源：

ONCOGENE | 2012年 / 31卷 / 25期

基金：

新加坡国家研究基金会;

关键词：

Smad3; miRNA-200; E-cadherin; ZEB1/2; gastric cancer; GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN GASTRIC-CANCER; II RECEPTOR GENE; TGF-BETA; MIR-200; FAMILY; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; REPRESSORS ZEB1; TUMOR INVASION;

D O I：

10.1038/onc.2011.484

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

To identify potential microRNA (miRNA) links between Smad3, a mediator of TGF-beta (transforming growth factor-beta) signaling, and E-cadherin, we characterized the miRNA profiles of two gastric cancer cell lines: SNU484-LPCX, which does not express Smad3, and SNU484-Smad3, in which Smad3 is overexpressed. We found that among differentially expressed miRNAs, miR-200 family members are overexpressed in SNU484-Smad3 cells. Subsequent studies, including analysis of the effects of silencing Smad3 in SNU484-Smad3 cells and a luciferase reporter assay, revealed that Smad3 directly binds to a Smad-binding element located in the promoter region of miR-200b/a, where it functions as a transcriptional activator. TGF-beta did not affect the regulatory role of Smad3 in transcription of miR-200 and expression of epithelial-mesenchymal transition markers. We conclude that Smad3 regulates, at the transcriptional level, miR-200 family members, which themselves regulate ZEB1 and ZEB2, known transcriptional repressors of E-cadherin, at the posttranscriptional level in a TGF-beta-independent manner. This represents a novel link between Smad3 and posttranscriptional regulation by miRNAs in epithelial-mesenchymal transition in gastric cancer cells. Oncogene (2012) 31, 3051-3059; doi: 10.1038/onc.2011.484; published online 24 October 2011

引用

页码：3051 / 3059

页数：9

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