In conclusion, our study revealed that c-MYC-activated MEG3 aggravates IR-induced AKI through activating mitophagy and promoting apoptosis by upregulation of RTKN in a miR-145-5p-dependent way to trigger the Wnt/β-Catenin pathway, which might offer a new insight into the therapeutic methods for IR-induced AKI in the future. Here, MYC is linked to acute kidney injury.