Estrogen upregulates nucleophosmin 1 expression in mouse uterus through MYC induction

Abstract

The uterus undergoes transcriptional changes regulated by estrogen and progesterone throughout the menstrual cycle. Although the estrogen-regulated transcriptome has been extensively studied, the implications of gene expression alterations are not fully elucidated. Our analysis of publicly available RNA-seq and ChIP-seq data revealed that estrogen upregulates genes involved in ribosome biogenesis and MYC pathway. Specifically, we observed increased expression of nucleophosmin 1 (NPM1), a key regulator of ribosome biogenesis with MYC-binding sites in its promoter, in estrogen-stimulated endometrial epithelium. Utilizing an estrogen receptor (ER) antagonist, we demonstrated that estrogen's upregulation of Npm1 and Myc in the uterus is dependent on ER activation. Further, estrogen treatment of isolated endometrial epithelium from the uterus confirmed an increase in Myc and Npm1 expression. The application of Myc siRNA attenuated the estrogen-induced Npm1 expression in the isolated epithelium. These findings suggest that estrogen-enhanced MYC expression, mediated by ER, may play a crucial role in Npm1 expression in the uterus. This, in turn, contributes to ribosome biogenesis, underscoring its significance in endometrial proliferation and thickening. Therefore, our findings offer significant insights into NPM1 role in normal endometrial physiology, highlighting the connection between estrogen-mediated transcriptional regulation and ribosome biogenesis in the uterus.