Huwe1 sustains normal ovarian epithelial cell transformation and tumor growth through the histone H1.3-H19 cascade
文献类型：期刊论文
| 作者 | Sun B8,9; Yan LZ5,8; Li L3,8; An SQ8,9; Jiang H1; Zou FD*7; Zhou XD*5,8; Zhang XH1; Cheng DM2; Yu XP2 |
| 刊名 | Cancer Research
 |
| 出版日期 | 2017 |
| 卷号 | **期号:**页码:Epub ahead of print |
| 关键词 | Huwe1 Ovarian Cancer H1.3 H19 Tumorigenesis |
| 英文摘要 | Ubiquitination-directed protein degradation is important in many cancers for tumor initiation and maintenance, and E3 ligases containing HECT domains are emerging as new therapeutic targets. In contrast to many other E3 ligases, the role of HUWE1 in ovarian cancer where HUWE1 is dysregulated has been unclear. Here we report that genetic deletion of Huwe1 in the mouse inhibits transformation of ovary surface epithelium cells without significantly affecting cell survival and apoptosis, and that Huwe1 deletion after tumors have been initiated inhibits tumor growth. In Huwe1-deficient cells, expression of histone H1.3 increased, inhibiting the expression of noncoding RNA H19. H19 silencing phenocopied the effects of Huwe1 deficiency, whereas H1.3 silencing partially rescued the expression of H19 and the Huwe1 null phenotype. Inducible silencing of HUWE1 in human ovarian cancer cells produced a similar phenotype. Mechanistically, HUWE1 bound and ubiquitinated H1.3, which was consequently marked for destruction by proteasomes. Our results establish that HUWE1 plays an essential role in promoting ovarian cancer. |
| 语种 | 英语 |
| 资助机构 | This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA 01040403), the National Natural Science Foundation of China (NSFC, 81171960), and the Top Talents Program of Yunnan Province, China (2012HA014) to X. Zhao. ; This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA 01040403), the National Natural Science Foundation of China (NSFC, 81171960), and the Top Talents Program of Yunnan Province, China (2012HA014) to X. Zhao. ; This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA 01040403), the National Natural Science Foundation of China (NSFC, 81171960), and the Top Talents Program of Yunnan Province, China (2012HA014) to X. Zhao. ; This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA 01040403), the National Natural Science Foundation of China (NSFC, 81171960), and the Top Talents Program of Yunnan Province, China (2012HA014) to X. Zhao. |
| 源URL | [http://159.226.149.26:8080/handle/152453/12028]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_肿瘤干细胞生物学 昆明动物研究所_中国科学院昆明灵长类研究中心 |
| 通讯作者 | zhaoxudong@mail.kiz.ac.cn; fundzou@scu.edu.cn |
| 作者单位 | 1.Department of Hematology/Oncology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong 510623, China 2.Chengdu Medical College, Chengdu, Sichuan 610500, China 3.School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China 4.Renji Hospital, Shanghai Jiaotong University, Shanghai 200120, China 5.Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 6.Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA 7.Key Laboratory of Bio-resources and Eco-environment, College of Life Sciences, Sichuan University, Chengdu 610064, Sichuan, PR China 8.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 9.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China |
| 推荐引用方式 GB/T 7714 | Sun B,Yan LZ,Li L,et al. Huwe1 sustains normal ovarian epithelial cell transformation and tumor growth through the histone H1.3-H19 cascade[J]. Cancer Research,2017,**(**):Epub ahead of print. |
| APA | Sun B.,Yan LZ.,Li L.,An SQ.,Jiang H.,...&Yang D.(2017).Huwe1 sustains normal ovarian epithelial cell transformation and tumor growth through the histone H1.3-H19 cascade.Cancer Research,**(**),Epub ahead of print. |
| MLA | Sun B,et al."Huwe1 sustains normal ovarian epithelial cell transformation and tumor growth through the histone H1.3-H19 cascade".Cancer Research **.**(2017):Epub ahead of print. |
入库方式： OAI收割
来源：昆明动物研究所
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