多囊卵巢综合征中转录因子的表达（英文）

Expression of transcription factors in polycystic ovary syndrome

摘要

目的 多囊卵巢综合征(polycystic ovary syndrome，PCOS)是影响女性健康的常见内分泌疾病。本研究通过生物信息学方法对比PCOS患者与正常研究对象之间基因及转录因子表达的差异，并验证关键转录因子的功能，以期为PCOS的发病机制研究提供新方向。 方法 利用生物信息学方法分析RNA测序数据集GSE168404中PCOS患者与正常研究对象之间的差异表达基因(differentially expressed genes，DEGs)及差异表达转录因子(differentially expressed transcription factors，DETFs)，并利用基因本体(Gene Ontology，GO)和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)进行功能富集分析，进一步在PCOS小鼠和正常对照小鼠的卵巢组织中通过蛋白质印迹法及逆转录实时定量聚合酶链式反应(reverse transcription quantitative polymerase chain reaction，RT-qPCR)验证核心转录因子的功能。 结果 通过对PCOS患者与正常研究对象的RNA数据集GSE168404进行生物信息学分析，共发现332个DEGs，其中259个DEGs在PCOS患者组表达上调，73个DEGs在PCOS患者组表达下调。进一步分析筛出19个DETFs，其中16个DETFs在PCOS患者组表达上调，3个DETFs在PCOS患者组表达下调。上调的DETFs(TFCP2L1，DACH1，ESR2，AFF3，SMAD9，ZNF331，HOPX，ATOH8，HIF3α，DPF3，HOXC4，HES1，ID1，JDP2，SOX4，和ID3)主要与脂质代谢、生长发育及细胞黏附相关。蛋白质印迹法和RT-qPCR结果表明：PCOS模型小鼠的低氧诱导因子(hypoxia-inducible factor，HIF)1α和HIF2α的蛋白质和mRNA的表达水平相比对照小鼠均显著下降，HIF3α则显著上升(均P<0.001)。 结论 PCOS患者与正常研究对象之间基因及转录因子的表达水平具有显著差异，转录因子HIF3α在PCOS中可能具有重要作用，可能成为PCOS诊断的新标志物及治疗的新靶点。

Abstract

Objective Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women’s health. This study aims to investigate gene and transcription factor (TF) expression differences between PCOS patients and healthy individuals using bioinformatics approaches, and to verify the function of key transcription factors, with the goal of providing new insights into the pathogenesis of PCOS. Methods Differentially expressed genes (DEGs) and differentially expressed transcription factors (DETFs) between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results A total of 332 DEGs were identified between PCOS patients and controls, including 259 upregulated and 73 downregulated genes in the PCOS group. 19 DETFs were further screened, of which 16 were upregulated and 3 were downregulated in PCOS. The upregulated DETFs (including TFCP2L1, DACH1, ESR2, AFF3, SMAD9, ZNF331, HOPX,ATOH8, HIF3α, DPF3, HOXC4, HES1, ID1, JDP2, SOX4, and ID3) were primarily associated with lipid metabolism, development, and cell adhesion. Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor (HIF) 1α and HIF2α, and significantly increased expression of HIF3α compared to control mice (all P<0.001). Conclusion Significant differences in gene and TF expression exist between PCOS patients and healthy individuals. HIF-3α may play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.

关键词

多囊卵巢综合征 / 转录因子 / 低氧诱导因子 / 调控网络 / 生物信息学

Key words

polycystic ovary syndrome / transcription factor / hypoxia-inducible factors / regulatory networks / bioinformatics