Ma Si-Rong, Ma Qi, Ma Ya-Nan, Zhou Wen-Jie
School of Clinical Medicine, Ningxia Medical University, Yinchuan, China.
Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, China.
Front Genet. 2023 Sep 14;14:1209042. doi: 10.3389/fgene.2023.1209042. eCollection 2023.
Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI. We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection. As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA-RNA interaction, including circRNA-miRNA and miRNA-mRNA co-expression networks. We finally created a circRNA-miRNA-mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein-protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2. To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.
脓毒症是一种复杂的、危及生命的临床综合征，可引发其他相关疾病，如急性肾损伤（AKI）。环状RNA（circRNA）是一类具有多种功能的非编码RNA，在微小RNA（miRNA）海绵作用中发挥重要作用。circRNA在多种疾病的发生发展中起重要作用。circRNA与竞争性内源RNA（ceRNA）调控网络是脓毒症相关性急性肾损伤（SAKI）发病和进展中的未知因素。本研究旨在阐明circRNA在SAKI中复杂的相关调控机制。我们收集了40例成人全血样本，其中包括20例SAKI患者和20例健康对照。此外，对5例样本进行了RNA测序分析，我们分别鉴定出差异表达的circRNA、miRNA和mRNA（分别为DEcircRNAs、DEmiRNAs和DEmRNAs）。所有样本均来自腹腔感染的SAKI患者。结果，我们筛选出236个DEcircRNAs、105个DEmiRNAs和4065个DEmRNAs。然后，我们基于RNA-RNA相互作用构建了两个共表达网络，包括circRNA-miRNA和miRNA-mRNA共表达网络。最后，通过合并这两个共表达网络创建了一个circRNA-miRNA-mRNA调控网络。功能和通路分析表明，ceRNA中的DEmRNAs主要集中在T细胞活化、中性粒细胞及其反应以及细胞因子方面。建立了蛋白质-蛋白质相互作用网络以筛选参与SAKI调控网络的关键基因。被确定为前10个节点的枢纽基因如下：锌指蛋白727（ZNF727）、肌动蛋白结合蛋白（MDFIC）、干扰素诱导跨膜蛋白2（IFITM2）、叉头框D4样蛋白6（FOXD4L6）、主要组织相容性复合体Ⅱ类反式激活因子（CIITA）、钾通道蛋白KCNE1B、肿瘤睾丸抗原BAGE2、肽基脯氨酰异构酶A4（PPIAL4A）、泛素特异性蛋白酶17样蛋白7（USP17L7）和丝氨酸蛋白酶2（PRSS2）。据我们所知，本研究是首次描述SAKI患者中circRNA、miRNA和mRNA表达谱变化的研究。这些发现为SAKI的治疗提供了新的治疗靶点，并为其发病机制提供了新的思路。
