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整合的计算机模拟和体外验证表明,LINC00963和SNHG15作为冠状动脉疾病的候选生物标志物。

Integrative in Silico and in vitro validation suggest LINC00963 and SNHG15 as candidate biomarkers for coronary artery disease.

作者信息

Saberiyan Mohammadreza, Noorabadi Parisa, Kahourian Ozra, Golestanifar Ahmad, Jafari Negar, Shahabi Rabori Venus, Mousavi Pegah

机构信息

Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

Sci Rep. 2025 Jul 1;15(1):21501. doi: 10.1038/s41598-025-08777-7.

Abstract

Despite notable advancements in prevention, medication, and treatment approaches, coronary artery disease (CAD) remains a significant challenge for healthcare systems and the economy. In relation to CAD, long non-coding RNAs (lncRNAs) can impact its development by influencing immune responses, affecting the functions of endothelial and vascular smooth muscle cells, and modifying lipid metabolism. Through the analysis of the GEO dataset (GSE42148), we identified differentially expressed genes (DEGs) and lncRNAs (DELs) in CAD patients. We performed functional enrichment and pathway analyses to clarify the roles of these DEGs. To investigate the interactions between DEGs and DELs, we created the lncRNA-mRNA interaction network. To investigate the interactions between DEGs and DELs, we constructed an lncRNA-mRNA interaction network. Candidate lncRNAs were validated by real-time PCR using peripheral blood from CAD patients. Our in vitro study confirmed that LINC00963 and SNHG15 were upregulated in CAD patients compared to the control group. Notably, LINC00963 levels were significantly elevated in patients with a positive family history, hyperlipidemia, hypertension, and diabetes, while SNHG15 expression was higher in smokers. Additionally, a significant negative correlation was found between the expressions of LINC00963 and SNHG15 and the age of the individuals. ROC curve analysis indicated that both lncRNAs have high sensitivity and specificity as biomarkers. Furthermore, this study suggests that LINC00963 and SNHG15 could serve as valuable markers for the early detection of CAD, particularly in younger individuals. It is proposed that these lncRNAs are associated with inflammatory conditions in CAD. Overall, LINC00963 and SNHG15 may act as promising early detection markers for CAD based on bioinformatics and peripheral blood-based validation.

摘要

尽管在预防、药物治疗和治疗方法方面取得了显著进展,但冠状动脉疾病(CAD)仍然是医疗系统和经济面临的重大挑战。关于CAD,长链非编码RNA(lncRNAs)可通过影响免疫反应、影响内皮细胞和血管平滑肌细胞的功能以及改变脂质代谢来影响其发展。通过对GEO数据集(GSE42148)的分析,我们在CAD患者中鉴定出差异表达基因(DEGs)和lncRNAs(DELs)。我们进行了功能富集和通路分析,以阐明这些DEGs的作用。为了研究DEGs和DELs之间的相互作用,我们构建了lncRNA-mRNA相互作用网络。使用CAD患者的外周血通过实时PCR对候选lncRNAs进行验证。我们的体外研究证实,与对照组相比,CAD患者中LINC00963和SNHG15上调。值得注意的是,有家族史阳性、高脂血症、高血压和糖尿病的患者中LINC00963水平显著升高,而吸烟者中SNHG15表达更高。此外,发现LINC00963和SNHG15的表达与个体年龄之间存在显著负相关。ROC曲线分析表明,这两种lncRNAs作为生物标志物均具有高敏感性和特异性。此外,本研究表明,LINC00963和SNHG15可作为CAD早期检测的有价值标志物,尤其是在年轻个体中。有人提出,这些lncRNAs与CAD中的炎症状态有关。总体而言,基于生物信息学和外周血验证,LINC00963和SNHG15可能作为CAD有前景的早期检测标志物。

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