Geronikolou Styliani, Pavlopoulou Athanasia, Koutelekos Ioannis, Kalogirou Dimitrios, Bacopoulou Flora, Cokkinos Dennis V
Clinical, Translational and Experimental Surgery Research Center, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece.
Center for Adolescent Medicine and UNESCO Chair in Adolescent Health Care, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Biomedicines. 2024 Oct 8;12(10):2280. doi: 10.3390/biomedicines12102280.
Recent literature suggests that ferroptosis (FPT) may be a key player in polycystic ovary syndrome (PCOS) pathogenesis, but the underlying mechanism(s) remain(s) unclear. Therefore, herein, we made an effort to reproduce the molecular signature of the syndrome by including FPT and exploring novel drug targets for PCOS. (a) Our previously constructed PCOS interactions molecular network was extended with the addition of FPT-associated genes (interaction score above 0.7) and (b) gene set enrichment analysis was performed so as to detect over-represented KEGG pathways. The updated interactome includes 140 molecules, 20 of which are predicted/novel, with an interaction score of 7.3, and 12 major hubs. Moreover, we identified 16 over-represented KEGG pathways, with FPT being the most overexpressed pathway. The FPT subnetwork is connected with the PCOS network through KDM1A. FPT cell death is involved in PCOS development, as its major hub TP53 was shown to be the most important hub in the whole PCOS interactome, hence representing a prioritized drug target.
近期文献表明，铁死亡（FPT）可能是多囊卵巢综合征（PCOS）发病机制中的关键因素，但其潜在机制仍不清楚。因此，在本文中，我们通过纳入铁死亡并探索PCOS的新药物靶点，努力重现该综合征的分子特征。（a）我们先前构建的PCOS相互作用分子网络通过添加与铁死亡相关的基因（相互作用得分高于0.7）进行了扩展，并且（b）进行了基因集富集分析，以检测过度富集的KEGG通路。更新后的相互作用组包括140个分子，其中20个是预测的/新的，相互作用得分为7.3，以及12个主要枢纽。此外，我们确定了16条过度富集的KEGG通路，其中铁死亡是表达最上调的通路。铁死亡细胞死亡参与PCOS的发展，因为其主要枢纽TP53被证明是整个PCOS相互作用组中最重要的枢纽，因此代表了一个优先的药物靶点。
