Pan Jing-Jing, Yang Yang, Chen Xiao-Qing, Shi Jia, Wang Mu-Zi, Tong Mei-Ling, Zhou Xiao-Guang
Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Department of Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Kaohsiung J Med Sci. 2023 Apr;39(4):337-344. doi: 10.1002/kjm2.12644. Epub 2023 Jan 19.
As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.
作为一种新型非编码RNA,环状RNA(circRNAs)参与不同的生物学过程。尽管越来越多的证据支持circRNAs在肾脏疾病中的重要作用,但在新生儿急性肾损伤(AKI)中其机制仍不清楚。采用高通量测序分析来研究缺氧诱导的AKI新生儿与对照组之间circRNAs的表达。进行生物信息学分析以预测差异表达circRNAs的功能。最后,通过定量实时PCR(qPCR)筛选并确定差异表达的circRNAs。(1)共鉴定出296个差异表达的circRNAs(折叠变化>2且p<0.05)。其中,184个circRNAs在AKI组中显著上调,112个显著下调。(2)通路分析表明泛素介导的蛋白水解、肾细胞癌、Jak-STAT和HIF-1信号通路参与了AKI。(3)选择折叠变化较高的前五个上调和五个下调的circRNAs进行qPCR验证。与对照组相比,hsa_circ_0008898(折叠变化=5.48,p=0.0376)和hsa_circ_0005519(折叠变化=4.65,p=0.0071)在窒息诱导的AKI组中显著上调,而hsa_circ_0132279(折叠变化=-4.47,p=0.0008)、hsa_circ_0112327(折叠变化=-4.26,p=0.0048)和hsa_circ_0017647(折叠变化=-4.15,p=0.0313)在窒息诱导的AKI组中显著下调。本研究有助于未来对新生儿AKI的研究,并促进新型治疗靶点的识别。