Department of Vascular Surgery, Huadong Hospital, Affiliated with Fudan University, Shanghai 200040, China.
Department of Vascular Surgery, Zhongshan Hospital, Affiliated with Fudan University, Shanghai 200032, China.
Biochem Biophys Res Commun. 2018 May 5;499(2):328-337. doi: 10.1016/j.bbrc.2018.03.156. Epub 2018 Mar 26.
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.
本研究旨在鉴定原发性大隐静脉曲张（PGSVV）中的异常 circRNA 表达，并探讨其潜在的临床意义。应用高通量测序分析了三组配对的 PGSVV 静脉样本和对照组中 circRNA 的差异表达。进一步进行了包括基因本体（GO）分析和基因组百科全书（KEGG）通路分析在内的计算生物信息学分析，以富集 microRNA 数据。使用实时定量逆转录聚合酶链反应（qRT-PCR）在所有静脉样本中验证了选定的异常 circRNAs，并绘制了受试者工作特征（ROC）曲线以评估诊断和潜在的临床意义。在 PGSVV 中，共有 232 个 circRNA 明显异常表达，包括 105 个上调和 127 个下调 circRNA。显著改变的 circRNA 预测的前 10 个下游 miRNA 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 分析显示，最丰富和有意义的生物过程、细胞成分和分子功能术语与分解代谢的调节、细胞质和 ATP 结合有关。KEGG 通路分析揭示的最丰富和有意义的途径与“轴突导向”、“维生素消化吸收”和“NF-Kappa B 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 组中的表达水平明显低于对照组，ROC 曲线下面积分别为 0.9091、0.8025 和 0.8148。本研究表明 circRNA 在 PGSVV 中差异表达，突出了 circRNA 在 PGSVV 发病机制中的关键作用，并表明 hsa_circ_0006427、hsa_circ_0089810 和 hsa_circ_0005267 可能是潜在的诊断和临床生物标志物。
