Abstract

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is closely associated with liver injury and ferroptosis. However, the molecular mechanisms underlying IH-induced liver damage remain largely unexplored. Here, we identify circ_38959 as a novel liver-protective circular RNA that mitigates IH-induced injury and ferroptosis. Circ_38959 overexpression in AML-12 hepatocytes significantly rescued cell viability, reduced apoptosis, and suppressed ferroptosis under IH conditions. Mechanistically, RNA immunoprecipitation uncovered that IGF2BP3 functions as a key interacting protein of circ_38959. Knocking down circ_38959 can down-regulate the protein expressions of IGF2BP3, c-Myc and c-Met. Functional studies revealed that IGF2BP3 deficiency abrogated the protective effects of circ_38959, confirming its essential role in liver protection and ferroptosis suppression. In an IH mouse model, AAV-mediated overexpression of circ_38959 effectively rescued liver function, and suppressed ferroptosis. Collectively, our study unveils a circ_38959-IGF2BP3 interaction that protects against IH-induced liver damage, highlighting circ_38959 as a potential therapeutic target for liver injury associated with OSA.