Hsa_circRNA_0045861通过微小RNA-181d-5p/沉默调节蛋白1信号轴促进肾盂输尿管连接处梗阻中的肾损伤。

Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis.

作者信息

Fan Xu, Yin Xiaoming, Zhao Qi, Yang Yi

机构信息

Department of Pediatric Urology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Ann Transl Med. 2021 Oct;9(20):1571. doi: 10.21037/atm-21-5060.

BACKGROUND

Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in children. This study explored the effects and the regulatory mechanisms of the circular RNA (circRNA) hsa_circRNA_0045861 (circRNA_0045861) in UPJO.

METHODS

RNA sequencing was used to identify the differentially expressed circRNAs in UPJO. The effects of circRNA_0045861 on renal cell apoptosis was investigated by flow cytometry and Western blot analysis. Furthermore, we used bioinformatics methods to predict the possible target genes of circRNA_0045861. Fluorescence hybridization and dual-luciferase reporter assays were performed to validate the target genes of circRNA_0045861. Finally, we evaluated the effects of circRNA_0045861 target gene miR-181d-5p on UPJO-induced renal fibrosis .

RESULTS

RNA sequencing identified 63 upregulated and 64 downregulated circRNAs in UPJO patients. The expression of circRNA_0045861 was significantly elevated in kidney damage both and . Silencing circ_0045861 inhibited transforming growth factor (TGF)-β1-induced apoptosis in human kidney 2 (HK-2) cells. Furthermore, circ_0045861 was shown to directly interact with the microRNA miR-181d-5p and regulate the expression of sirtuin 1 (SIRT1), thereby promoting the progression of apoptosis and renal injury. In addition, overexpression of miR-181d-5p inhibited cell apoptosis and renal fibrosis in a mouse model through downregulating the SIRT1/p53 pathway.

CONCLUSIONS

Circ_0045861 may be a novel candidate circRNA in the pathogenesis of UPJO by acting as a pro-apoptotic factor via the miR-181d-5p/SIRT1 axis.

背景

肾盂输尿管连接部梗阻（UPJO）是儿童肾积水最常见的病因之一。本研究探讨环状RNA（circRNA）hsa_circRNA_0045861（circRNA_0045861）在UPJO中的作用及其调控机制。

方法

采用RNA测序鉴定UPJO中差异表达的circRNA。通过流式细胞术和蛋白质免疫印迹分析研究circRNA_0045861对肾细胞凋亡的影响。此外，我们使用生物信息学方法预测circRNA_0045861可能的靶基因。进行荧光杂交和双荧光素酶报告基因检测以验证circRNA_0045861的靶基因。最后，我们评估了circRNA_0045861靶基因miR-181d-5p对UPJO诱导的肾纤维化的影响。

结果

RNA测序鉴定出UPJO患者中有63种上调和64种下调的circRNA。circRNA_0045861的表达在肾损伤中均显著升高。沉默circ_0045861可抑制转化生长因子（TGF）-β1诱导的人肾2（HK-2）细胞凋亡。此外，circ_0045861被证明可直接与微小RNA miR-181d-5p相互作用并调节沉默调节蛋白1（SIRT1）的表达，从而促进细胞凋亡和肾损伤的进展。此外，miR-181d-5p的过表达通过下调SIRT1/p53通路抑制小鼠模型中的细胞凋亡和肾纤维化。