Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.
Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.
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DOI：
10.2147/pgpm.s424359
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发表时间：
2023
影响因子：
1.9
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中科院分区：
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动脉闭塞症（阿索）是非创伤性下肢截肢的主要原因。大量研究表明，环状RNA（circular RNA，circRNA）在肿瘤和心血管疾病中发挥着重要的调控作用。然而，circRNA在阿索形成和发展中的潜在作用和病理机制仍不清楚。本研究采用基因芯片技术研究了正常下肢动脉和阿索动脉中circRNA的表达谱。利用KEGG数据库进行生物信息学分析，研究差异表达circRNA（DE circRNA）的富集情况并预测其功能。通过使用RT-qPCR评估前5个上调和5个下调的circRNA（正常组的原始密度≥200）的表达来验证微阵列测定的准确性。利用软件进一步预测了circRNA-miRNA-mRNA相互作用网络。与正常下肢相比，HE和EVG染色显示阿索动脉呈纤维膜增生和管腔狭窄。共鉴定出12，735个circRNA，其中包括1196个DE circRNA，其中276个在阿索组中上调，920个下调。|log2（FC）|> 1且padj < 0.05。RT-qPCR证实，在所选的10种circRNA中，hsa_circ_0003266、hsa_circ_0118936和hsa_circ_0067161在ASO组中上调，而hsa_circ_0091934和hsa_circ_0092022在阿索组中下调（p < 0.05）。GO分析表明DE circRNA主要富集在蛋白结合、细胞内部分和细胞器组织中。KEGG通路分析表明，MAPK信号通路、人类T细胞白血病病毒1型感染、肿瘤中的蛋白多糖与DE circRNA相关。circRNA-miRNA-mRNA相互作用网络揭示了mRNA和与circRNA连接的miRNA在阿索中起着不可或缺的作用。本研究描述了人阿索动脉中circRNA的表达谱，为进一步研究circRNA在阿索形成和发展中的调控机制提供了分子基础。
Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct. This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO. This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.