LUCAT1 inhibits ferroptosis in bladder cancer by regulating the mRNA stability of STAT3

Object: In this study, we aimed to elucidate the role of LUCAT1, a recently identified lncRNA, in ferroptosis within the context of bladder cancer (BC).Methods: Through a comprehensive array of experimental techniques, including transmission electron microscopy (TEM), RNA pull-down assays, and fluorescence in situ hybridization (FISH), we investigated the molecular interactions and functional consequences associated with LUCAT1 in BC cells.Results: Our findings indicate that LUCAT1 acts as a pivotal regulator in BC, fostering cell proliferation, migration, and invasion, while concurrently impeding ferroptosis. Mechanistically, we unveiled a direct binding between LUCAT1 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which governs the mRNA stability of signal transducer and activator of transcription 3 (STAT3). Intriguingly, ectopic expression of STAT3 counteracted the suppressive effect of LUCAT1 on ferroptosis induction in BC cells. Notably, in an in vivo setting, LUCAT1 emerged as a crucial modulator of ferroptosis inhibition in BC by regulating STAT3 mRNA stability. Conclusion: Collectively, our study identifies LUCAT1 as a novel oncogenic player, repressing ferroptosis in BC. These findings shed light on the intricate interplay between lncRNAs and ferroptosis in cancer, implicating LUCAT1 as a promising therapeutic target for patients afflicted with BC. Further investigations into the under-lying mechanisms governing LUCAT1-mediated ferroptosis resistance are warranted, with the potential to un-cover novel strategies for combating BC progression and improving patient outcomes.

Automated summary

This study reveals the role of LUCAT1 in bladder cancer (BC) and its impact on ferroptosis. LUCAT1 acts as a regulator in BC, promoting cell proliferation, migration, and invasion while inhibiting ferroptosis. Mechanistically, LUCAT1 binds to IGF2BP1, which governs STAT3 mRNA stability.