ALKBH5-Mediated m6A Modification Drives Apoptosis in Renal Tubular Epithelial Cells by Negatively Regulating MUC1

• DOI: 10.1007/s12033-024-01250-2
• Publication Date: 2024-08-23T14:55:52Z
• Authors: Wenwei Chen; Changyi Liu; Yanfeng He; Tao Jiang; Qin Chen; Hua Zhang; Rui Gao
• Keywords: MUC1

Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m6A) modification has been extensively studied and associated with various pathologic processes, research on its specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m6A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly decreased the m6A level on the mRNA of Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5 impaired the stability of MUC1 mRNA in RTECs, leading to attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis.