Wan Qi-Quan, Wu Di, Ye Qi-Fa
Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Department of Transplant Surgery, The Third Xiangya Hospital, Central South University, Changsha 410013, China; Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):684-689. doi: 10.1016/j.bbrc.2017.08.131. Epub 2017 Aug 31.
The development of circular RNA (circRNA) microarray has facilitated the study of the role of circRNAs in regulating gene expression through a circRNA-miRNA-mRNA network. In our study, microarray was performed to detect the expression profiles of circRNAs during lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Twenty rats were randomly divided into 2 groups, the control group and the LPS group, 10 rats in each group. Three rats each from both groups were randomly selected. Using circRNA microarray data, we compared the circRNA expression profiles in lung tissues between these 6 rats. The most differentially expressed circRNA species from these profiles were validated and optimized as ARDS biomarkers and potential therapeutic targets. Overall, 395 and 562 circRNAs were significantly up- and down-regulated in LPS group vs. control group, respectively. Six up-regulated and 4 down-regulated circRNAs from the top 10 candidates were eventually selected to be validated. Among them, only 4 up-regulated circRNAs (mmu_circRNA_19423, rno_circRNA_010489, rno_circRNA_011426, mmu_circRNA_30664) and 1 down-regulated circRNA (rno_circRNA_005564) exhibited significant validation. The 5 highest ranking target miRNAs of these 5 validated circRNAs were predicted according to the miRNA support vector regression method. This is the first study to investigate circRNA expression profile and a large number of aberrantly expressed circRNAs were revealed during ARDS. The significantly over- or under-expressed circRNA may represent a novel biomarker and be developed as a novel therapeutic target for the clinical management of ARDS. The results are preliminary and need to be confirmed in further well-designed studies with larger sample size.
环状RNA(circRNA)微阵列的发展促进了对circRNAs通过circRNA- miRNA- mRNA网络调控基因表达作用的研究。在我们的研究中,进行微阵列检测脂多糖(LPS)诱导的急性呼吸窘迫综合征(ARDS)期间circRNAs的表达谱。20只大鼠随机分为2组,对照组和LPS组,每组10只大鼠。每组随机选取3只大鼠。利用circRNA微阵列数据,我们比较了这6只大鼠肺组织中的circRNA表达谱。这些表达谱中差异表达最显著的circRNA种类被验证并优化为ARDS生物标志物和潜在治疗靶点。总体而言,与对照组相比,LPS组分别有395和562种circRNAs显著上调和下调。最终从排名前十的候选物中选择6种上调和4种下调的circRNAs进行验证。其中,只有4种上调的circRNAs(mmu_circRNA_19423、rno_circRNA_010489、rno_circRNA_011426、mmu_circRNA_30664)和1种下调的circRNA(rno_circRNA_005564)表现出显著的验证结果。根据miRNA支持向量回归方法预测了这5种验证的circRNAs的5个排名最高的靶miRNA。这是第一项研究ARDS期间circRNA表达谱的研究,揭示了大量异常表达的circRNAs。显著过表达或低表达的circRNA可能代表一种新型生物标志物,并可开发为ARDS临床管理的新型治疗靶点。结果是初步的,需要在样本量更大的进一步精心设计的研究中得到证实。