Recent studies indicate that circular RNAs are involved in dysregulation of kidney injury. Nevertheless, the underlying mechanisms remain largely unclear. Therefore, this study sought to investigate the role of circ-USP1 in the pathogenesis of early renal allografts. Thirty-two male C57BL/6J mice aged between 6 and 8 weeks were divided into the sham and allograft groups. Thereafter, the association between miR-194-5p, circ-USP1 and DNMT3A was confirmed using a combination of bioinformatics and the luciferase reporter gene assay. Additionally, the expression of circ-USP1, miR-194-5p and DNMT3A mRNA was detected through qPCR. Afterwards, the Western blot assay was performed to examine the expression of DNMT3A protein. Finally, the TUNEL assay was conducted to determine the rate of apoptosis in DNMT3A cells. The expression of circ-USP1 increased, while that of miR-194-5p decreased in renal allografts. Additionally, silencing circ-USP1 reduced kidney injuries caused by renal allografts in mice. Moreover, miR-194-5p was a target for circ-USP1, and DNMT3A was a target of miR-194-5p. Finally, it was shown that silencing circ-USP1 reduced DNMT3A expression in the kidney of mice that received renal allografts. Circ-USP1 functions as a competing endogenous RNA for miR-194-5p. This occurs in order to regulate DNMT3A expression in kidney injury induced by hypoxia in acute renal allografts.

中文翻译：

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沉默circ-USP1通过调节急性肾移植中的miR-194-5p/DNMT3A轴保护肾小管免受缺氧诱导的肾损伤

最近的研究表明，环状 RNA 与肾损伤的失调有关。然而，潜在的机制仍然在很大程度上不清楚。因此，本研究旨在探讨 circ-USP1 在早期同种异体肾移植发病机制中的作用。32 只 6 至 8 周龄的雄性 C57BL/6J 小鼠被分为假手术组和同种异体移植组。此后，使用生物信息学和荧光素酶报告基因检测的组合证实了 miR-194-5p、circ-USP1 和 DNMT3A 之间的关联。此外，通过qPCR检测circ-USP1、miR-194-5p和DNMT3A mRNA的表达。之后，进行蛋白质印迹测定以检查DNMT3A蛋白的表达。最后，进行 TUNEL 测定以确定 DNMT3A 细胞的凋亡率。circ-USP1 的表达增加，而 miR-194-5p 在同种异体肾移植中降低。此外，沉默 circ-USP1 减少了小鼠肾移植引起的肾损伤。此外，miR-194-5p 是 circ-USP1 的靶标，DNMT3A 是 miR-194-5p 的靶标。最后，表明沉默 circ-USP1 降低了接受同种异体肾移植的小鼠肾脏中 DNMT3A 的表达。Circ-USP1 作为 miR-194-5p 的竞争性内源 RNA 起作用。发生这种情况是为了调节急性肾同种异体移植物中缺氧诱导的肾损伤中 DNMT3A 的表达。结果表明，沉默 circ-USP1 会降低接受同种异体肾移植的小鼠肾脏中 DNMT3A 的表达。Circ-USP1 作为 miR-194-5p 的竞争性内源 RNA 起作用。发生这种情况是为了调节急性肾同种异体移植物中缺氧诱导的肾损伤中 DNMT3A 的表达。结果表明，沉默 circ-USP1 会降低接受同种异体肾移植的小鼠肾脏中 DNMT3A 的表达。Circ-USP1 作为 miR-194-5p 的竞争性内源 RNA 起作用。发生这种情况是为了调节急性肾同种异体移植物中缺氧诱导的肾损伤中 DNMT3A 的表达。