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 p27Kip1, 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.