河马信号通路
细胞生物学
信号转导
新陈代谢
细胞内
机制(生物学)
生物
癌症研究
化学
生物化学
认识论
哲学
作者
Xinyu He,Xuemei Fan,Lei Qu,Xiang Wang,Li Jiang,Lingjie Sang,Chengyu Shi,Siyi Lin,Jie-Cheng Yang,Zuozhen Yang,Kai Lei,Junhong Li,Huai-Qiang Ju,Qingfeng Yan,J. Liu,Fudi Wang,Jian‐Zhong Shao,Yan Xiong,Wenqi Wang,Aifu Lin
标识
DOI:10.1038/s41467-023-37871-5
摘要
Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.
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