Microarray Expression Profile and Bioinformatic Analysis of Circular RNA in Human Arteriosclerosis Obliterans.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-10-24 eCollection Date: 2023-01-01 DOI:10.2147/PGPM.S424359
Yu Zhou, Huoying Cai, Lin Huang, Mingshan Wang, Ruiming Liu, Siwen Wang, Yuansen Qin, Chen Yao, Zuojun Hu
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Abstract

Background: 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.

Methods and results: 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.

Conclusion: 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.

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人类动脉硬化闭塞症患者环状RNA的微阵列表达谱和生物信息学分析。
背景:闭塞性动脉硬化症(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起着重要的调节作用。然而,circRNAs在ASO形成和发展中的潜在作用和病理机制仍不清楚。方法和结果:本研究采用微阵列分析方法研究circRNAs在正常下肢动脉和ASO动脉中的表达情况。使用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。使用软件进一步预测了circRNA-miRNA-mRNA相互作用网络。与正常下肢组相比,HE和EVG染色的ASO动脉表现为纤维膜增生和管腔狭窄。基于|log2(FC)|>1和padj<0.05,共鉴定出12735个circRNA,其中1196个DE circRNA在ASO组中276个上调,920个下调。在选定的10个circRNA中,RT-qPCR证实ASO组的hsa_cir_0003266、hsa_ccirc_0118936和hsa_cCirc_0067161上调,而hsa_crc_0091934和hsa\rc_0092022下调(p<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T细胞白血病病毒1型感染、癌症蛋白多糖和DE circRNAs有关。circRNA-miRNA-mRNA相互作用网络显示,mRNAs和与circRNAs连接的miRNAs在ASO中都发挥着不可或缺的作用。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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