Clinical application of doxorubicin (Dox) is limited due to its serious side effects including nephrotoxicity, and kidney podocytes play important roles in renal diseases. MicroRNAs (miRNAs) are critical regulators associated with human diseases. The purpose of this study was to explore a novel target in adjusting Dox-induced renal podocyte injury. Through a double luciferase reporter gene experiment, it was found that miR-874-3p directly targeted methionine sulfoxide reductase B3 (MsrB3). During the tests of miR-874-3p inhibitor and MsrB3 siRNA in human podocytes or miR-874-3p antagomir in mice, we found that the expression levels of downstream oxidative stress and apoptosis-related proteins were regulated by miR-874-3p/MsrB3 signal to alleviate or aggravate renal podocyte injury. The data in the present work showed that miR-874-3p aggravated Dox-caused renal podocyte injury by promoting apoptosis and oxidative damage via inhibiting MsrB3. Therefore, miR-874-3p/MsrB3 should be considered as a new therapeutic target in controlling renal podocyte injury induced by Dox.

中文翻译：

---

MicroRNA-874-3p通过靶向甲硫氨酸亚砜还原酶B3加重阿霉素诱导的肾足细胞损伤。

阿霉素（Dox）的临床应用由于其严重的副作用（包括肾毒性）而受到限制，并且肾脏足细胞在肾脏疾病中起重要作用。微小RNA（miRNA）是与人类疾病相关的关键调节因子。这项研究的目的是探索在调整Dox诱导的肾足细胞损伤中的新目标。通过双重荧光素酶报告基因实验，发现miR-874-3p直接靶向蛋氨酸亚砜还原酶B3（MsrB3）。在小鼠足细胞或miR-874-3p antagomir中的miR-874-3p抑制剂和MsrB3 siRNA的测试中，我们发现miR-874-3p /调节下游氧化应激和凋亡相关蛋白的表达水平。 MsrB3信号减轻或加重了肾脏足细胞损伤。目前工作中的数据表明，miR-874-3p通过抑制MsrB3促进细胞凋亡和氧化损伤，从而加剧了Dox引起的肾足细胞损伤。因此，miR-874-3p / MsrB3应被视为控制Dox引起的肾足细胞损伤的新治疗靶点。