MicroRNA-107 alleviates ferroptosis-mediated acute kidney injury by regulating the PI3K/Akt/mTOR pathway

Mechanistic pathways and biomarkers need to be explored to elucidate the pathogenesis of acute kidney injury (AKI). This study examined miR-107 expression in AKI and the molecular mechanisms underlying the regulation of ferroptosis-mediated AKI.

This study included 30 patients with AKI and 30 healthy individuals in the control group. The miR-107 serum expression levels were determined using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The HK-2 cells were subjected to ferroptosis in vitro, and a AKI mice model to study the effect of miR-107 in vivo. After RNA overexpression, malondialdehyde (MDA), lipid reactive oxygen species (ROS), and glutathione (GSH) levels were measured. Additionally, the regulatory relationship between miR-107 and its downstream pathway genes was analyzed.

The down-regulated expression of miR-107 detected in the serum of patients with AKI suggested its utility as a potential diagnostic indicator for AKI. Moreover, miR-107 expression was down-regulated in both HK-2 cell models of AKI and HK-2 cell ferroptosis model. Upregulation of miR-107 decreased MDA expression and increased GSH expression in erastin (Era)-induced ferroptosis in HK-2 cells in vitro. Additional, AKI mice exhibited down-regulated expression levels of miR-107, and the ROS, MDA, and GSH expression changes in AKI mice were rescued after miR-107 overexpressed, which was consistent with the effect of Fer-1 treatment. Furthermore, the PI3K/Akt/mTOR pathway exhibited a correlation with miR-107 expression in Era-induced ferroptosis in HK-2 cells.

In summary, miR-107 is expressed at low levels in AKI and can inhibit ferroptosis in HK-2 cells, which may play a protective role against AKI.