期刊
ONCOTARGET
卷 5, 期 21, 页码 10621-10635出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2524
关键词
Ikaros; CD133; hepatocellular carcinoma; cancer stem cells
资金
- National Key Program for Basic Research of China (973) [2015CB553905]
- National Natural Science Foundation of China [81472726, 81272438, 81301859, 81372192]
- Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning
- National Key Sci-Tech Special Project of China [2013ZX10002-011]
- SKLORG Research foundation [91-13-02, 91-14-09]
CD133 is a cellular surface glycoprotein that has been reported as a marker for the enrichment of cancer stem cells (CSCs). However, the regulatory mechanism of CD133 remains unknown. CSCs have been proposed to contribute to radioresistance and multi-drug resistance. The elucidation of key regulators of CD133 and CSCs is critical for the development of CSC-targeted therapy. In this study, we showed that Ikaros inhibited the expression of CD133 via direct binding to the CD133 P1 promoter and repressed the tumorigenic and self-renewal capacity of CD133(+) cancer stem-like cells in hepatocellular carcinoma (HCC). We found that Ikaros interacted with CtBP as a transcription repressor complex, which inhibited CD133 expression in HCC. We also demonstrated that Ikaros expression was up-regulated by ETS1 which activity was regulated by MAPKs pathway. Furthermore, decreased expression of Ikaros was significantly associated with poor survival in HCC patients. Overall, our study identifies that Ikaros plays a role as a transcription repressor in HCC and is a new reactivated therapeutic target for the treatment of HCC. Meanwhile, our findings provide evidence that Ikaros could be an attractive inhibitor of the target gene CD133, which reactivates anticancer mechanisms in targeted CSC therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据