Background
Acute-on-chronic liver failure (ACLF) is a syndrome with both high prevalence and mortality. However, the underlying mechanisms remain elusive and there is no effective therapeutic approach available. Here we
Conclusion
We reveal a novel molecular mechanism that IGF2BP3/HIF1A/YAP signaling promotes hepatocyte reprogramming, causing hepatic injury in ACLF. Our study provides potential targets for treatment of ACLF.
Results
Our data demonstrated that IGF2BP3 recognized m6A modification in HIF1A mRNA as an m6A reader, thereby promoting expression of HIF1A by increasing RNA stability. HIF1A activated Rho GTPases (RhoA) and suppressed phosphorylation of YAP via inhibiting LATS1/2, promoting translocation of non-phosphorylated YAP into the nucleus, resulting in fetal liver programme and ultimate hepatic injury in ACLF patients.