The cooperative regulation of miR ‐221 by APE1 and AUF1 impacts p27 Kip1 defining a miR signature relevant for cervical cancer

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is a multifunctional protein involved in DNA repair, transcriptional regulation, and redox signaling, which significantly contributes to cancer progression and chemoresistance. Recent studies revealed a new role in RNA metabolism, specifically influencing the processing of some onco‐microRNAs (miRs). The interaction of APE1 with AU‐rich element RNA‐binding protein 1 (AUF1) is crucial in regulating RNA stability under oxidative stress conditions. Our research shows that APE1 and AUF1 bind pre‐miR‐221, preferentially once oxidized, thus affecting miR‐221 maturation and impacting gene transcription, such as the cyclin‐dependent kinase inhibitor p27 Kip1 , which is essential for tumor suppression and cell cycle regulation. Moreover, we identified a 13‐miR signature, comprising miRs regulated by both APE1 and AUF1, that exhibits strong prognostic value in cervical cancer. These findings suggest a novel potential role of both APE1 and AUF1 as therapeutic targets in cervical cancer.