LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression
文献类型：期刊论文
| 作者 | Dong, Zheng; Gao, Ming; Li, Changying; Xu, Ming; Liu, Sijin |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2020-06 |
| 卷号 | 7期号:11页码:1-16 |
| 关键词 | arsenic cell cycle arrest enhancer of zeste homolog 2 (EZH2) lncRNA tumorigenesis urothelial cancer associated 1 (UCA1) |
| 英文摘要 | Arsenic (As) is a widespread metalloid contaminant, and its internal exposure is demonstrated to cause serious detrimental health problems. Albeit considerable studies are performed to interrogate the molecular mechanisms responsible for As-induced toxicities, the exact mechanisms are not fully understood yet, especially at the epigenetic regulation level. In the present study, it is identified that long non-coding RNA (lncRNA) urothelial cancer associated 1 (UCA1) alleviates As-induced G2/M phase arrest in human liver cells. Intensive mechanistic investigations illustrate that UCA1 interacts with enhancer of zeste homolog 2 (EZH2) and accelerates the latter's protein turnover rate under normal and As-exposure conditions. The phosphorylation of EZH2 at the Thr-487 site by cyclin dependent kinase 1 (CDK1) is responsible for As-induced EZH2 protein degradation, and UCA1 enhances this process through increasing the interaction between CDK1 and EZH2. As a consequence, the cell cycle regulator nuclear factor of activated T cells 2 (NFATc2), a downstream target of EZH2, is upregulated to resist As-blocked cell cycle progress and cytotoxicity. In conclusion, the findings decipher a novel prosurvival signaling pathway underlying As toxicity from the perspective of epigenetic regulation: UCA1 facilitates the ubiquitination of EZH2 to upregulate NFATc2 and further antagonizes As-induced cell cycle arrest. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/44724]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Dong, Zheng,Gao, Ming,Li, Changying,et al. LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression[J]. ADVANCED SCIENCE,2020,7(11):1-16. |
| APA | Dong, Zheng,Gao, Ming,Li, Changying,Xu, Ming,&Liu, Sijin.(2020).LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression.ADVANCED SCIENCE,7(11),1-16. |
| MLA | Dong, Zheng,et al."LncRNA UCA1 Antagonizes Arsenic-Induced Cell Cycle Arrest through Destabilizing EZH2 and Facilitating NFATc2 Expression".ADVANCED SCIENCE 7.11(2020):1-16. |
入库方式： OAI收割
来源：生态环境研究中心
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