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LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
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LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
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Journal Article
LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
2023
Overview
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.
Iron metabolism dysregulation is associated with various diseases including cancer. Here, the authors show that one iron-triggered lncRNA
LncRIM
regulates cellular iron metabolism effectively by wiring up the Hippo-YAP signaling pathway and promotes breast cancer development.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 59
/ 64
/ 82/1
/ 82/29
/ 82/51
/ 82/83
/ 96/109
/ 96/31
/ Copper
/ Divalent metal transporter-1
/ Humanities and Social Sciences
/ Humans
/ Iron
/ RNA, Long Noncoding - genetics
/ RNA, Long Noncoding - metabolism
/ Science
/ Signal Transduction - physiology
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Wiring
