期刊
ONCOGENE
卷 31, 期 25, 页码 3051-3059出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.484
关键词
Smad3; miRNA-200; E-cadherin; ZEB1/2; gastric cancer
资金
- National Research Foundation
- Korea government (MEST) [KRF-2008-313-C00676, 2009-0081756, 2009-0081789]
- department of gastroenterology, Gachon University Gil Hospital
- National Research Foundation of Korea [2009-0081789] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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
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