基因敲除
癌症研究
细胞凋亡
下调和上调
表观遗传学
生物
细胞生长
基因
遗传学
作者
Tong Han,Yukang Wu,Xiang Hu,Yaqi Chen,Wenwen Jia,Qizhi He,Yiding Bian,Mengfei Wang,Xudong Guo,Jiuhong Kang,Yiran Li
标识
DOI:10.1038/s41419-020-2674-y
摘要
Abstract Long noncoding RNAs (lncRNAs) are emerging as critical regulators in tumor initiation and progression. However, the biological mechanisms and potential clinical application of lncRNA NORAD in endometrial cancer (EC) remain unknown. Herein, we identified NORAD underwent promoter hypermethylation-associated downregulation in EC. Epigenetic inactivation of NORAD was correlated with EC progression (FIGO stage) and poor outcome. Overexpression of NORAD significantly inhibited cell growth and promoted apoptosis in EC cells. Mechanistic studies revealed that multiple regions of NORAD served as a platform for binding with the central domain of anti-apoptotic factor FUBP1. Our findings further indicated that the NORAD/FUBP1 interaction attenuated FUBP1 nuclear localization and thus impaired the occupancies of FUBP1 on its target pro-apoptotic gene promoters, resulting in apoptosis induction in EC. Moreover, knockdown of NORAD promoted tumor growth in the xenograft mice model. While, introduction of NORAD-4 fragment, which bound with FUBP1, successfully reversed tumor growth and apoptosis inhibition mediated by NORAD knockdown in vivo. Our findings provide mechanistic insight into the critical roles of NORAD as a tumor suppressor in EC progression. NORAD could possibly serve as a novel prognostic biomarker and provide the rationale for EC therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI