BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT antagonist IDAX
| Autor: | Feiyue Yu, Yabing Liu, Chuanyi Zhou, Shangfu Li, Hui Zeng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colorectal cancer Carcinogenesis Primary Cell Culture Biophysics macromolecular substances Biology medicine.disease_cause Biochemistry Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cell Line Tumor medicine Gene silencing Humans RNA Small Interfering Promoter Regions Genetic Molecular Biology Transcription factor Wnt Signaling Pathway Cell Proliferation Polycomb Repressive Complex 1 Cell growth Wnt signaling pathway Epithelial Cells Cell Biology medicine.disease DNA-Binding Proteins Gene Expression Regulation Neoplastic 030104 developmental biology BMI1 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Protein Binding Transcription Factors |
| Zdroj: | Biochemical and biophysical research communications. 496(2) |
| ISSN: | 1090-2104 |
| Popis: | Aberrant activation of Wnt signaling plays a critical role in the development of colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is upregulated in various types of cancer and contributes to epigenetic silencing of tumor suppressors. In this study, we showed that BMI1 is upregulated in colon cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in colon cancer cells represses these effects. We also found that BMI1 binds to the promoter of IDAX, a Wnt antagonist, and decreases its transcription. Expression of IDAX is downregulated in colon cancer tissues and cell lines and negatively correlated with BMI1 in colon cancer tissues. Furthermore, Silencing of IDAX counteracts the effects of BMI1 suppression, while its overexpression reverses oncogenic effects of BMI1. Together, these findings indicate that BMI1-mediated IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis, suggesting that BMI1∖IDAX axis as a potential novel diagnostic and therapeutic target of colon cancer. |
| Databáze: | OpenAIRE |
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