Ameliorative effects of miR-186 on cisplatin-triggered acute kidney injury via targeting ZEB1.

Cisplatin is a commonly used chemotherapy drug in cancers, which can lead to acute kidney injury (AKI). AKI can occur in almost one third of tumor patients, who receive cisplatin treatment. microRNAs (miRNAs) are significant tools in regulating the expression of crucial factors in multiple diseases, but little is known about their biological roles in AKI. As exhibited, miR-186 has been observed to be down-regulated in tumors. Our study concentrated on the function of miR-186 in cisplatin-triggered AKI. Here, we reported miR-186 was considerably decreased in the serum samples from AKI patients compared with those from the healthy controls. Additionally, we found in NRK-52E cells exposed to 6 mM cisplatin, miR-186 was greatly decreased time-dependently. Meanwhile, an AKI model in rats was successfully set in our study. Levels of serum creatinine and blood urea nitrogen were significantly induced by cisplatin exposure. In AKI rat models, miR-186 exhibited a rapid decrease in both the serum and the kidney tissues. Then, miR-186 overexpression improved NRK-52E cell proliferation and protected NRK-52E cells against cisplatin-triggered apoptosis. Furthermore, ZEB1 was identified and confirmed as a target gene of miR-186. It has been demonstrated that ZEB1 exerts crucial roles in the development of AKI. As evidenced in our current study, ZEB1 was remarkably elevated in AKI patients and AKI rat models. Moreover, ZEB1 was induced by indicated doses of cisplatin in different time periods in NRK-52E cells. ZEB1 inhibition rescued the reduced proliferation and increased apoptosis of NRK-52E cells. In conclusion, loss miR-186 expression contributed to cisplatin-induced AKI, partly through targeting ZEB1. miR-186 might be provided as an effective biomarker for AKI via targeting ZEB1.