Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran; Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.
Comput Biol Med. 2023 Mar;154:106601. doi: 10.1016/j.compbiomed.2023.106601. Epub 2023 Jan 24.
Polycystic ovary syndrome (PCOS) is one of the most incident reproductive diseases, and remains the main cause of female infertility. Granulosa cells play a critical role in normal follicle development and steroid hormones synthesis. In spite of extensive research, no sole medication has been approved by FDA to treat PCOS. This study aimed to investigate the novel therapeutics targets in PCOS, focusing on granulosa cells transcriptome functional analysis with a drug repositioning approach.
PCOS microarray and RNA-Seq datasets in granulosa cells were screened and reanalyzed. KEGG pathway enrichment and interaction network analyses were performed and followed by a set of drug signature screening and Poly-pharmacology survey.
545 deregulated genes were identified via filters including p < 0.05 and |log2FC| > 1. Amongst the top 15 KEGG pathways significantly enriched, metabolism of xenobiotics by cytochrome P450, steroid hormone biosynthesis and ovarian steroidogenesis were observed. The Protein-Protein Interaction network identified 18 hub genes amongst this set. Interestingly, most candidate drug signatures have been introduced by databases are either FDA approved or entered into clinical trials, including melatonin, resveratrol and raloxifene. Investigational or experimental introduced drugs obey rules of drug-likeness with almost safe and acceptable ADMET properties. Notably, 21 top target genes of the final drug set were also included in the granulosa significant differentially expressed genes.
Results of the current study represent approved, investigational and experimental drug signatures according to the differentially expressed genes in granulosa cells with supported literature reviews. This data might be useful for researchers and clinicians to pave the way for better management of PCOS.
多囊卵巢综合征（PCOS）是最常见的生殖系统疾病之一，也是女性不孕的主要原因。颗粒细胞在正常卵泡发育和类固醇激素合成中起着关键作用。尽管进行了广泛的研究，但 FDA 尚未批准任何单一药物用于治疗 PCOS。本研究旨在探讨 PCOS 的新治疗靶点，重点是通过药物再定位方法对颗粒细胞转录组功能进行分析。
筛选和重新分析了 PCOS 颗粒细胞的微阵列和 RNA-Seq 数据集。进行了 KEGG 通路富集和相互作用网络分析，随后进行了一组药物特征筛选和多药效学调查。
通过包括 p<0.05 和 |log2FC|>1 的过滤器，鉴定出 545 个差异表达基因。在显著富集的前 15 个 KEGG 通路中，观察到细胞色素 P450 介导的外来物代谢、甾体激素生物合成和卵巢甾体生成。该蛋白质-蛋白质相互作用网络确定了这一组中的 18 个枢纽基因。有趣的是，大多数候选药物特征已被数据库引入，包括褪黑素、白藜芦醇和雷洛昔芬，这些药物要么已获得 FDA 批准，要么已进入临床试验。具有良好的药物相似性和可接受的 ADMET 特性的研究性或实验性引入药物也在其中。值得注意的是，最终药物集的 21 个顶级靶基因也包含在颗粒细胞中差异表达的基因中。
根据颗粒细胞中差异表达基因的研究结果代表了已批准、研究性和实验性的药物特征，并得到了文献综述的支持。这些数据可能对研究人员和临床医生有帮助，为更好地管理 PCOS 铺平道路。
