Regulatory networks of circRNA- centred ceRNAs in sepsis-induced acute kidney injury.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2023-12-01 Epub Date: 2023-11-18 DOI:10.1080/15592294.2023.2278960
Tongtong Ma, Junjie Wu, Zhongqing Chen
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引用次数: 0

Abstract

Sepsis is the primary cause of acute kidney injury (AKI) and is associated with high mortality rates. Growing evidence suggests that noncoding RNAs are vitally involved in kidney illnesses, whereas the role of circular RNAs (circRNAs) in sepsis-induced AKI (SAKI) remains largely unknown. In this present study, caecal ligation and puncture (CLP) in mice was performed to establish an SAKI model. The expression of circRNAs and mRNAs was analysed using circRNA microarray or next-generation sequencing. The results revealed that the expressions of 197 circRNAs and 2509 mRNAs were dysregulated. Validation of the selected circRNAs was performed by qRT-PCR. Bioinformatics analyses and chromatin immunoprecipitation demonstrated that NF-κB/p65 signalling induced the upregulation of circC3, circZbtb16, and circFkbp5 and their linear counterparts by p65 transcription in mouse tubular epithelial cells (mTECs). Furthermore, competitive endogenous RNA (ceRNA) networks demonstrated that some components of NF-κB signalling were potential targets of these dysregulated circRNAs. Among them, Tnf-α was increased by circFkbp5 through the downregulation of miR-760-3p in lipopolysaccharide (LPS)-stimulated mTECs. Knocking down circFkbp5 inhibited the p65 phosphorylation and apoptosis in injured mTECs. These findings suggest that the selected circRNAs and the related ceRNA networks provide new knowledge into the fundamental mechanism of SAKI and circFkbp5/miR-760-3p/Tnf-α axis might be therapeutic targets.

以circRNA为中心的cerna在败血症诱导的急性肾损伤中的调控网络。
脓毒症是急性肾损伤(AKI)的主要原因,并与高死亡率相关。越来越多的证据表明,非编码rna在肾脏疾病中起着至关重要的作用,而环状rna (circRNAs)在脓毒症诱导的AKI (SAKI)中的作用仍然很大程度上未知。本研究采用小鼠盲肠结扎穿刺法(CLP)建立SAKI模型。使用circRNA微阵列或下一代测序分析circRNA和mrna的表达。结果显示,197个circrna和2509个mrna表达异常。通过qRT-PCR对所选环状rna进行验证。生物信息学分析和染色质免疫沉淀表明,NF-κB/p65信号通过p65转录诱导小鼠小管上皮细胞(mTECs)中circC3、circZbtb16和circFkbp5及其线性对应物的上调。此外,竞争性内源性RNA (ceRNA)网络表明,NF-κB信号传导的某些成分是这些失调环状RNA的潜在靶点。其中,在脂多糖(LPS)刺激的mTECs中,circFkbp5通过下调miR-760-3p使Tnf-α升高。敲除circFkbp5抑制p65磷酸化和损伤mtec的凋亡。这些发现表明,所选择的circrna和相关的ceRNA网络为SAKI的基本机制提供了新的知识,circFkbp5/miR-760-3p/Tnf-α轴可能是治疗靶点。
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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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