Polycystic Ovary Syndrome and Ferroptosis: Following Ariadne's Thread.

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.