Smad3 regulates E-cadherin via miRNA-200 pathway
- Authors
- Ahn, S-M; Cha, J-Y; Kim, J.; Kim, D.; Trang, H. T. H.; Kim, Y-M; Cho, Y-H; Park, D.; Hong, S.
- Issue Date
- Jun-2012
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- Smad3; miRNA-200; E-cadherin; ZEB1/2; gastric cancer
- Citation
- ONCOGENE, v.31, no.25, pp.3051 - 3059
- Journal Title
- ONCOGENE
- Volume
- 31
- Number
- 25
- Start Page
- 3051
- End Page
- 3059
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16365
- DOI
- 10.1038/onc.2011.484
- ISSN
- 0950-9232
- Abstract
- 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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