期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 298, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2022.102630
关键词
-
资金
- National Natural Science Foundation of China
- Zhejiang Provincial Natural Science Foundation
- Zhejiang Medical and health Science and Technology Project
- [81802975]
- [LY18H180010]
- [LY22H160045]
- [2019KY361]
- [2020KY101]
This study found that HOTAIR plays a role in promoting self-renewal and tumor propagation of breast cancer stem cells. HOTAIR recruits the PRC2 protein complex to inhibit the expression of IKBa, leading to activation of the NF-KB signaling pathway and promoting the expression of c-Myc and Cyclin D1. Clinical data analysis also showed that breast cancer patients with high HOTAIR expression have a lower survival rate.
Breast cancer is the most prevalent cancer among women, and it is characterized by a high rate of tumor development and heterogeneity. Breast cancer stem cells (CSCs) may well contribute to these pathological properties, but the mechanisms underlying their self-renewal and maintenance are still elusive. Here, we found that the long noncoding RNA HOTAIR is highly expressed in breast CSCs. HOTAIR is required for breast CSC self-renewal and tumor propagation. Mechanistically, we demonstrate that HOTAIR recruits the PRC2 protein complex to the promoter of IKBa to inhibit its expression, leading to activation of the NF-KB signaling pathway. The activated NF-KB signaling promotes downstream c-Myc and Cyclin D1 expression. Furthermore, our analysis of clinical samples from the GEPIA database indicated that the IKBa level, as well as the survival rate of patients, with high HOTAIR expression was significantly lower than that of patients with relatively low HOTAIR expression. Our data suggest that HOTAIR-mediated NF-KB signaling primes breast CSC selfrenewal and tumor propagation. In sum, we have identified HOTAIR-based NF-KB signaling regulatory circuit that promotes tumorigenic activity in breast CSCs, further indicating that HOTAIR could be a promising target for clinical treatment of breast cancers.
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