Identification of potential causal genes and drug targets in pulmonary hypertension based on transcriptomic analysis and Mendelian randomization.

IF 3.6 4区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Chengliang Liu, Fanliang Meng
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引用次数: 0

Abstract

Purpose: Currently, there is no definitive treatment for pulmonary hypertension (PH). This study aims to utilize the GEO database and conduct Mendelian randomization (MR) analysis to identify new genetic targets for PH and investigate their potential pathogenic pathways and therapeutic drugs.

Methods: We identified key genes by combining the findings from MR and bioinformatics analyses of GEO datasets. We performed enrichment analysis to explore the functional roles of these key genes. Then, we constructed protein-protein interaction (PPI) and miRNA-mRNA networks to identify interacting proteins and miRNAs. Drug prediction analysis was conducted to propose potential therapeutic drugs. Finally, we validated the results through the GEO dataset, RT-PCR, and western blot experiments.

Results: The joint analysis utilizing GEO databases and MR analysis identified two key genes, ITGA2B and TSPAN9 that exhibited significance across both analytical methods. The enrichment analysis indicated that the key genes were involved in critical biological functions and pathways, including cell adhesion, platelet activation, and the PI3K-Akt signaling pathway. The PPI and miRNA-mRNA networks further highlighted the significance of the key genes in PH. Drug prediction analysis revealed the potential of the key genes as therapeutic targets. The RT-PCR and western blot experiments validated the above findings.

Conclusion: By integrating bioinformatics and MR analysis, we found that ITGA2B and TSPAN9 have a causal relationship with PH. Our findings offer new insights into the molecular mechanism and potential treatment targets of PH, establishing a basis for future research and clinical applications.

基于转录组学分析和孟德尔随机化的肺动脉高压潜在致病基因和药物靶点鉴定。
目的:目前,肺动脉高压(PH)没有明确的治疗方法。本研究旨在利用GEO数据库,进行孟德尔随机化(Mendelian randomization, MR)分析,寻找新的PH基因靶点,并研究其潜在的致病途径和治疗药物。方法:结合GEO数据集的MR和生物信息学分析结果,确定关键基因。我们通过富集分析来探索这些关键基因的功能作用。然后,我们构建了蛋白-蛋白相互作用(PPI)和miRNA-mRNA网络来鉴定相互作用的蛋白和mirna。进行药物预测分析,提出潜在的治疗药物。最后,我们通过GEO数据集、RT-PCR和western blot实验验证了结果。结果:利用GEO数据库和MR分析的联合分析确定了两个关键基因ITGA2B和TSPAN9,这两个基因在两种分析方法中都表现出显著性。富集分析表明,这些关键基因参与细胞粘附、血小板活化、PI3K-Akt信号通路等关键生物学功能和通路。PPI和miRNA-mRNA网络进一步强调了关键基因在ph中的重要意义,药物预测分析揭示了关键基因作为治疗靶点的潜力。RT-PCR和western blot实验验证了上述发现。结论:结合生物信息学和MR分析,我们发现ITGA2B和TSPAN9与PH存在因果关系,为PH的分子机制和潜在治疗靶点提供了新的认识,为今后的研究和临床应用奠定了基础。
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来源期刊
Postgraduate Medical Journal
Postgraduate Medical Journal 医学-医学:内科
CiteScore
8.50
自引率
2.00%
发文量
131
审稿时长
2.5 months
期刊介绍: Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.
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