LncRNA Modulates Hippo-YAP Signaling to Reprogram Iron Metabolism

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 20

PMID 37080959

Authors

Xin-Yu He

Xiao Fan

Lei Qu

Xiang Wang

Li Jiang

Ling-Jie Sang

Cheng-Yu Shi

Siyi Lin

Jie-Cheng Yang

Zuo-Zhen Yang

Kai Lei

Jun-Hong Li

Huai-Qiang Ju

Qingfeng Yan

Jian Liu

Fudi Wang

Jianzhong Shao

Yan Xiong

Wenqi Wang

Aifu Lin

Affiliations

Soon will be listed here.

Abstract

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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