SRC involves in lysosomal function and regulates ferroptosis in polycystic ovary syndrome.

Abstract

Background: The pathogenesis of polycystic ovary syndrome (PCOS) is still unknown, so finding the molecular mechanisms of pathogenesis is crucial in PCOS.

Methods: The GSE34526 dataset from the Gene Expression Omnibus (GEO) database was used to screen biomarkers in this study. KEGG enrichment analysis of GSE34526 was performed using Gene Set Enrichment Analysis (GSEA). The differentially expressed genes(DEGs) were screened and analyzed for lysosome-related genes. Subsequently, further KEGG and GO analyses were performed, and it was found that it was enriched in the ferroptosis pathway, and then the ferroptosis-related differential genes were obtained. The genes at the core position were obtained by the Protein-Protein Interaction(PPI) network. We then focused our attention on SRC and verified the differential expression of SRC in ovarian tissues of hyperandrogenemic, hyperlipemic and control groups, as well as the differences in conception rate and litter rate of each group by rat test.

Results: GSEA analysis of the gene dataset GSE34526 revealed that LYSOSOME was significantly enriched in the PCOS group. There were 188 lysosome-related differentially expressed genes(LRDEGs) in granulosa cells from patients with PCOS, and 41 ferroptosis-related differentially expressed genes(FRDEGs). It was found that six of these genes, SRC, NCF2, SLC2A8, FTL, SLC2A6, SLC3A2, were present in all three datasets. SRC was the top ranked gene in the PPI network of FRDEGs.As verified by the rat model, the expression of SRC in the ovarian tissues of the hyperandrogenemic group was significantly higher than that of the control group (P=0.004) and the hyperlipemic group (P=0.002).

Conclusion: SRC, as an important gene involved in lysosomal function and regulating ferroptosis, is expected to be a potential target for PCOS.