Plasma miRNAs in polycystic ovary syndrome drive endometrial cancer progression: insights into molecular pathways and therapeutic targets

• DOI: 10.1007/s12672-025-01861-4
• Publication Date: 2025-02-07T17:40:08Z
• Authors: Xuedan Lai; Ling Wu; Peihong Lin; Lijiao You; Jianwen Ye
• Keywords: Clusterin

Polycystic ovary syndrome (PCOS) is a known risk factor for uterine endometrial cancer (UCEC), but its underlying mechanisms remain unclear. MicroRNAs (miRNAs) could provide insights into these and reveal potential therapeutic targets. Differential miRNA expression was analyzed in plasma exosomes from 15 PCOS control samples. Survival analysis assessed the prognostic value of miRNAs UCEC. MiRNA-target gene interaction networks co-expression analyses were used to explore molecular mechanisms. Validation performed using experimental data Ishikawa cells treated with six candidate drugs. Among differentially expressed miRNAs, 12 up-regulated 3 down-regulated PCOS. Twelve associated UCEC overall survival, miR-142, miR-424, miR-331 acting as protective factors, while remaining 9 identified factors. network highlighted key genes such PHF8, LCOR, SFT2D3, E2F1, ESR1, which found be patient survival. Further based on miR-424 miR-330 revealed significant alterations cellular processes related Two-sample Mendelian randomization causal relationships between AURKA or Testosterone estradiol might have adverse roles UCEC, drugs like troglitazone, valproic acid, retinoic progesterone demonstrated various effects processes. Our findings suggest that aberrant expression, particularly may play crucial progression. The serve targets further research required validate their clinical applications.