Abstract
Through comprehensive analysis of long non-coding RNA expression profiles from RNA-Seq data, we identified that MIR22HG was significantly downregulated in lung adenocarcinoma and associated with poor patient prognosis. Subsequent animal studies confirmed its tumor-suppressive effects. We elucidated the mechanism by which MIR22HG exerts oncogenic suppression in lung adenocarcinoma, revealing that it mediates Beclin1 to activate signaling pathways for both autophagy and ferroptosis, thereby producing a combined oncogenic suppressive effect. Additionally, we demonstrated that SIN3A directly binds to MIR22HG, leading to its downregulation. This interaction inhibits both autophagy and ferroptosis via the MIR22HG network, contributing to a pro-oncogenic effect. These findings propose MIR22HG as a novel diagnostic, prognostic, and therapeutic marker for lung cancer. Furthermore, targeting the repressive effects of SIN3A on MIR22HG expression may enhance dual-targeted therapy approaches in clinical settings.