Fan Xu, Yin Xiaoming, Zhao Qi, Yang Yi
Department of Pediatric Urology, Shengjing Hospital of China Medical University, Shenyang, China.
Ann Transl Med. 2021 Oct;9(20):1571. doi: 10.21037/atm-21-5060.
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.
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 .
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.
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.
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。
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。
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。
Circ_0045861可能是UPJO发病机制中的一种新型候选circRNA，它通过miR-181d-5p/SIRT1轴作为促凋亡因子发挥作用。
