BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT antagonist IDAX
- Department of Radiation Oncology, Yueyang Second People's Hospital, Yueyang 414000 (China)
- The 3rd Division of Oncology of the People's Hospital of Huangpi District and the Third Affiliated Hospital of Jianghan University, Wuhan 430300 (China)
Highlights: • BMI1 is upregulated and activates WNT signaling in colon cancer. • IDAX is a direct target of BMI1 and is downregulated in colon cancer. • IDAX plays as a tumor suppressor in colon cancer through inhibiting WNT signaling. 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.
- OSTI ID:
- 23127408
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 496, Issue 2; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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