Quan Kewei, Ning Shuting, You Zilin, Deng Gaopi
Department of Obstetrics and Gynecology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, 523000, China.
The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Heliyon. 2024 Aug 23;10(17):e36706. doi: 10.1016/j.heliyon.2024.e36706. eCollection 2024 Sep 15.
Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder affecting women of reproductive age. The pathogenesis of PCOS is influenced by factors such as race, genetics, environment, hyperandrogenemia, hyperinsulinemia, and obesity. However, the molecular mechanisms linking RNA modification and PCOS remain underexplored. This study aims to investigate the potential genetic and molecular pathways connecting RNA modification with PCOS through bioinformatics analyses.
The GSE34526, GSE5850, and GSE98421 datasets were obtained from the National Center for Biotechnology Information Gene Expression Omnibus database. We identified intersecting differentially expressed genes (DEGs) and RNA modification-related genes within the GSE34526 dataset and visualized the overlaps using a Venn diagram. Subsequent analyses included Gene Ontology (GO), pathway enrichment (Kyoto Encyclopedia of Genes and Genomes), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis. Additionally, we constructed a protein-protein interaction network as well as mRNA-miRNA, mRNA-RNA binding protein, and mRNA-transcription factor (TF) regulatory networks. The expression and receiver operating characteristic curves of hub genes were also identified.
The expression of several RNA modification-related DEGs (RMRDEGs) (, , , , and ) showed significant differences in PCOS patients. GSEA and GSVA indicated that RMRDEGs were enriched in the hedgehog, MAPK, JAK STAT, and Notch pathways. Key transcription factors, including SP7, KLF8, HCFC1, IRF1, and MLLT1, were identified in the TF regulatory networks.
These findings suggest that there are gene and miRNA profile alterations exist in PCOS patients and highlight immune-related differences. This knowledge could pave the way for new research directions in the diagnosis and treatment of PCOS.
多囊卵巢综合征（PCOS）是影响育龄女性的最常见的代谢和内分泌紊乱疾病。PCOS的发病机制受种族、遗传、环境、高雄激素血症、高胰岛素血症和肥胖等因素影响。然而，RNA修饰与PCOS之间的分子机制仍未得到充分探索。本研究旨在通过生物信息学分析探讨将RNA修饰与PCOS联系起来的潜在遗传和分子途径。
从美国国立生物技术信息中心基因表达综合数据库中获取GSE34526、GSE5850和GSE98421数据集。我们在GSE34526数据集中鉴定出相交的差异表达基因（DEGs）和RNA修饰相关基因，并使用维恩图可视化重叠情况。后续分析包括基因本体论（GO）、通路富集（京都基因与基因组百科全书）、基因集富集分析（GSEA）、基因集变异分析（GSVA）和免疫浸润分析。此外，我们构建了蛋白质-蛋白质相互作用网络以及mRNA- miRNA、mRNA-RNA结合蛋白和mRNA-转录因子（TF）调控网络。还鉴定了枢纽基因的表达和受试者工作特征曲线。
几个RNA修饰相关的差异表达基因（RMRDEGs）（、、、和）在PCOS患者中的表达存在显著差异。GSEA和GSVA表明RMRDEGs在刺猬、丝裂原活化蛋白激酶（MAPK）、Janus激酶信号转导和转录激活因子（JAK STAT）以及Notch通路中富集。在TF调控网络中鉴定出关键转录因子，包括SP7、KLF8、HCFC1、IRF1和MLLT1。
这些发现表明PCOS患者存在基因和miRNA谱改变，并突出了免疫相关差异。这些知识可为PCOS的诊断和治疗开辟新的研究方向。
