Zhou Yu, Cai Huoying, Huang Lin, Wang Mingshan, Liu Ruiming, Wang Siwen, Qin Yuansen, Yao Chen, Hu Zuojun
Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Laboratory of Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
Pharmgenomics Pers Med. 2023 Oct 24;16:913-924. doi: 10.2147/PGPM.S424359. eCollection 2023.
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 ( < 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.
闭塞性动脉硬化（ASO）是非创伤性下肢截肢的主要原因。多项研究表明，环状RNA（circRNA）在癌症和心血管疾病中发挥着重要的调节功能。然而，circRNA在ASO形成和发展中的潜在作用及病理机制仍不明确。
本研究采用微阵列分析来研究正常下肢动脉和ASO动脉中circRNA的表达谱。利用KEGG数据库进行生物信息学分析，以研究差异表达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（正常组原始密度≥200）的表达来验证微阵列检测的准确性。使用软件进一步预测circRNA- miRNA- mRNA相互作用网络。与正常下肢组相比，HE和EVG染色的ASO动脉呈现增生性纤维膜和管腔狭窄。共鉴定出12735个circRNA，基于|log2（FC）|>1和padj<0.05，在ASO组中包括1196个DE circRNA，其中276个上调，920个下调。在选定的10个circRNA中，RT-qPCR证实hsa_circ_0003266、hsa_circ_0118936和hsa_circ_0067161在ASO组中上调，而hsa_circ_0091934和hsa_circ_0092022下调（<0.05）。GO分析表明，DE circRNA主要富集于蛋白质结合、细胞内部分和细胞器组织。KEGG通路分析表明，MAPK信号通路、人类T细胞白血病病毒1感染、癌症中的蛋白聚糖与DE circRNA相关。circRNA- miRNA- mRNA相互作用网络显示，与circRNA相关的mRNA和miRNA在ASO中都发挥着不可或缺的作用。
本研究描述了人ASO动脉中circRNA的表达谱，并揭示了进一步研究circRNA在ASO形成和发展中调节机制的分子背景。
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