Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiles of HT29 cells in which REG4 expression was suppressed.


ABSTRACT: GATA6 is a zinc finger transcription factor that is required for the proliferation, development and specific gene regulation in the gastrointestinal tract. We have recently reported that GATA6-mediated induction of the intestinal stem cell marker LGR5 is required for the tumorigenicity of colon cancer cells. However, knockdown of LGR5, unlike GATA6, does not affect the proliferation of these cells under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is a target of GATA6. We further demonstrate that REG4 is downregulated by overexpression of miR-363, which suppresses GATA6 expression. Moreover, we show that GATA6-mediated activation of REG4 causes an acceleration of the growth of colon cancer cells under adherent conditions. These results suggest that GATA6 simultaneously activates the transcription of genes required for growth (REG4) and clonogenicity (LGR5), and the miR-363-GATA6-REG4/LGR5 pathway is critical for colorectal tumorigenesis. HT29 cells were transfected with a siRNA targeting REG4.

ORGANISM(S): Homo sapiens

SUBMITTER: Testu Akiyama 

PROVIDER: E-GEOD-62318 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

REG4 is a transcriptional target of GATA6 and is essential for colorectal tumorigenesis.

Kawasaki Yoshihiro Y   Matsumura Kosuke K   Miyamoto Masaya M   Tsuji Shinnosuke S   Okuno Masumi M   Suda Sakiko S   Hiyoshi Masaya M   Kitayama Joji J   Akiyama Tetsu T  

Scientific reports 20150921


The transcription factor GATA6 is a critical regulator of cell proliferation and development in the gastrointestinal tract. We have recently reported that GATA6 induces the expression of the intestinal stem cell marker LGR5 and enhances the clonogenicity and tumorigenicity of colon cancer cells, but not the growth of these cells cultured under adherent conditions. Here we show that REG4, a member of the regenerating islet-derived (REG) family, is also a target of GATA6. We further demonstrate th  ...[more]

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