Identification of aberrant circular RNA expression and its potential clinical value in primary great saphenous vein varicosities
Identification of aberrant circular RNA expression and its potential clinical value in primary great saphenous vein varicosities
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原发性大隐静脉曲张异常环状RNA表达的鉴定及其潜在临床价值
DOI：
10.1016/j.bbrc.2018.03.156
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发表时间：
2018
影响因子：
3.1
通讯作者：
Fu Weiguo
中科院分区：
文献类型：
--
作者：
Zhang Wan;Li Li;Si Yi;Shi Zhenyu;Zhu Ting;Zhuang Shunjiu;Fu Weiguo
本研究旨在检测原发性大隐静脉曲张(PGSVV)中CircRNA的异常表达，并探讨其潜在的临床意义。应用高通量测序技术分析3例PGSVV配对静脉标本和1例对照组CircRNA的差异表达。计算生物信息学分析，包括基因本体论(GO)分析和基因和基因组百科全书(KEGG)途径分析，进一步丰富了microRNA数据。用实时定量逆转录-聚合酶链式反应(qRT-PCR)验证所有静脉样本中异常的CircRNA，并绘制受试者工作特征(ROC)曲线以评价其诊断和潜在的临床意义。在PGSVV中，共有232个CircRNA显著异常表达，其中上调和下调的CircRNA分别为105和127个。预测的前10位下游miRNA分别是hsa-miR-103a-2-5p、hsa-miR-141-5p、hsa-miR-3692-5p、hsa-miR-4659a-3p、hsa-miR-4659b-3p、hsa-miR-4691-5p、hsa-miR-4778-3p、hsa-miR-6738-3p、hsa-miR-6792-3p和hsa-miR-6873-3p。GO分析表明，最丰富和最有意义的生物过程、细胞组成和分子功能项分别与分解代谢过程、细胞质和ATP结合的调节有关。KEGG通路分析揭示的最丰富和最有意义的通路与“轴突引导”、“维生素消化吸收”和“核因子-kappaB信号通路”有关。HSA_CIRC_0006427(P = 0.007)、hSA_CIRC_0089810(P = 0.044)和hSA_CIRC_0005267(P = 0.049)在pGSVV组的表达水平较对照组显著下调，其ROC曲线下面积分别为0.9091、0.8025和0.8148。本研究证实了CircRNAs在PGSVV中的差异表达，强调了CircRNAs在PGSVV发病机制中的重要作用，提示hSA_CIRC_0006427、hSA_CIRC_0089810和hSA_CIRC_0005267可能是潜在的诊断和临床生物学标志物。
This study aimed to identify aberrant circRNA expression in primary great saphenous vein varicosities (PGSVVs) and investigate its potential clinical significance. High-throughput sequencing was applied to analyze the differential expression of circRNAs in three paired vein samples of PGSVVs and a control group. Computational bioinformatics analyses, including gene ontology (GO) analysis and encyclopedia of genes and genomes (KEGG) pathway analysis, were performed to further enrich microRNA data. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the selected aberrant circRNAs in all vein samples, and a receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic and potential clinical significance. A total of 232 circRNAs were significantly aberrantly expressed in PGSVVs, including 105 and 127 upregulated and downregulated circRNAs, respectively. The predicted top 10 downstream miRNAs of the significantly altered circRNAs are hsa-miR-103a-2-5p, hsa-miR-141-5p, hsa-miR-3692-5p, hsa-miR-4659a-3p, hsa-miR-4659b-3p, hsa-miR-4691-5p, hsa-miR-4778-3p, hsa-miR-6738-3p, hsa-miR-6792-3p and hsa-miR-6873-3p. GO analysis revealed that the most enriched and meaningful biological process, cellular component, and molecular function terms were related to the regulation of catabolic processes, the cytoplasm and ATP binding, respectively. The most enriched and meaningful pathways revealed by KEGG pathway analysis were related to “axon guidance” “vitamin digestion and absorption” and “NF-Kappa B signaling pathway”. Hsa_circ_0006427 (P = 0.007), hsa_circ_0089810 (P = 0.044) and hsa_circ_0005267 (P = 0.049) were significantly downregulated in the PGSVV group relative to their expression levels in the control group, and the area under the ROC curve was 0.9091, 0.8025 and 0.8148, respectively. This study demonstrated that circRNAs were differentially expressed in PGSVVs, and highlights the crucial roles of circRNAs in the pathogenesis of PGSVVs and indicates that hsa_circ_0006427, hsa_circ_0089810 and hsa_circ_0005267 might be potential diagnostic and clinical biological markers.