Screening, identification, and experimental validation of SUMOylation biomarkers in Parkinson's disease.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-08-08 DOI:10.1186/s41065-025-00525-1

Yifo Wei, Xinning Zhang, Rui Zuo, Wenxin Dang, Lu Chen, Fan Liu, Jia Yao, Weizheng Ran, Zhigang Chen, Xiaoyan Wang, Furong Lv, Yue Yu

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引用次数: 0

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. The role of protein post-translational modifications (PTMs), especially small ubiquitin-like modifier (SUMO) conjugation (SUMOylation), in PD pathogenesis remains unclear. This study aimed to investigate the relationship between SUMOylation and PD.

Methods: The analysis included the GSE22491 dataset, GSE18838 dataset, and 189 SUMO related genes. Differentially expressed genes (DEGs) between the PD group and the control group were identified in GSE22491; these were then intersected with SUMO related genes to identify candidate genes. Machine learning was used to select biomarkers consistent across both datasets, which were validated in GSE6631. Further analyses included back propagation (BP) neural network analysis, enrichment analysis, immune infiltration analysis, regulatory network construction, drug prediction, and molecular docking. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the biomarkers.

Results: An overlap analysis of 3,222 DEGs and 189 SUMO related genes identified 25 candidate genes. Subsequent validation using the GSE22491 and GSE18838 datasets narrowed these biomarkers down to SUMO3 and SEH1L, which are involved in pathways (such as the nuclear pore pathway) associated with PD. Significant positive correlations were observed between specific immune cell subtypes and both biomarkers. Based on these correlations, relevant transcription factors (ZNF394, IRF4, FOXM1, EGR1) and drugs (Cianidanol, Methylmethanesulfonate, Valproic acid) were predicted. Additionally, RT-qPCR results confirmed that SUMO3 is significantly downregulated in PD.

Conclusion: SUMO3 and SEH1L were identified as novel biomarkers for PD, offering potential targets for early diagnosis and therapy in PD.

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帕金森病SUMOylation生物标志物的筛选、鉴定和实验验证

背景：帕金森病（PD）是一种常见的神经退行性疾病。蛋白质翻译后修饰（PTMs），特别是小泛素样修饰（SUMO）偶联（SUMO化）在PD发病机制中的作用尚不清楚。本研究旨在探讨SUMOylation与PD之间的关系。方法：分析GSE22491数据集、GSE18838数据集和189个SUMO相关基因。PD组与对照组在GSE22491中发现差异表达基因（DEGs）；然后将这些基因与SUMO相关基因交叉以鉴定候选基因。机器学习用于选择两个数据集一致的生物标志物，并在GSE6631中进行了验证。进一步分析包括反向传播（BP）神经网络分析、富集分析、免疫浸润分析、调控网络构建、药物预测、分子对接等。采用逆转录-定量聚合酶链反应（RT-qPCR）验证生物标志物。结果：对3222个deg和189个SUMO相关基因进行重叠分析，鉴定出25个候选基因。随后使用GSE22491和GSE18838数据集进行验证，将这些生物标记物缩小到SUMO3和SEH1L，它们参与与PD相关的途径（如核孔途径）。特异性免疫细胞亚型与两种生物标志物之间存在显著正相关。基于这些相关性，预测相关转录因子（ZNF394、IRF4、FOXM1、EGR1）和药物（Cianidanol、甲磺酸、丙戊酸）。此外，RT-qPCR结果证实，SUMO3在PD中显著下调。结论：SUMO3和SEH1L是PD的新型生物标志物，为PD的早期诊断和治疗提供了潜在的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.