MiR-144-3p regulates cell proliferation and apoptosis in renal ischemia-reperfusion injury by targeting EZH2.

Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury, with limited effective therapeutic options. While microRNAs (miRNAs) play crucial roles in regulating various diseases, including renal IRI, their specific targets and mechanisms remain elusive. In this study, hypoxia/reoxygenation (H/R) significantly promoted apoptosis in both NRK-52E and HK-2 cells, accompanied by a marked downregulation of miR-144-3p in both H/R-treated cells and the kidneys of mice subjected to ischemia/reperfusion (I/R) injury. Moreover, miR-144-3p overexpression enhanced cell viability under H/R conditions, as evidenced by the results of MTT assays. Dual-luciferase reporter assays identified EZH2 as a direct target of miR-144-3p, while Western blot analysis revealed that miR-144-3p suppressed EZH2 protein expression. Furthermore, EZH2 knockdown reduced Bax and cleaved Caspase-3 expression, highlighting its role in apoptosis regulation. Finally, miR-144-3p protected against renal IRI by inhibiting apoptosis and promoting cell proliferation by modulating EZH2, offering novel insights into its protective mechanisms. These findings position EZH2 as a potential therapeutic target for mitigating renal IRI.