Exploring the potential role of ENPP2 in polycystic ovary syndrome and endometrial cancer through bioinformatic analysis

The datasets TCGA-UCEC (pertaining to EC), GSE34526, GSE137684, and GSE6798 (related to PCOS) were procured and subjected to analysis. The gene <i>ENPP2</i> has been recognized as the shared element connecting PCOS and EC. Next, we observed a significant downregulation of <i>ENPP2</i> expression in the granulosa cells in PCOS compared to the normal patients, while an upregulation of <i>ENPP2</i> expression was observed in the endometrium of hyperandrogenic PCOS patients relative to the normal. <i>In vitro</i>, the WB revealed that 5-dihydrotestosterone (DHT) upregulated <i>ENPP2</i> expression in Ishikawa and HEC-1-A cells. Additionally, we found that <i>ENPP2</i> promoted the proliferation, migration, and invasion of Ishikawa and HEC-1-A cells. Subsequently, we discovered that overexpressed <i>ENPP2</i> may lead to an increase in <i>CYP19A1</i> (aromatase) and <i>AR</i> mRNA level. IF demonstrated that <i>ENPP2</i> increased the expression of <i>AR</i>, suggesting a regulatory role for <i>ENPP2</i> in hormonal response within PCOS and EC. Our findings indicated a significant correlation between <i>ENPP2</i> expression and the modulation of immune responses.