SIRT1 upregulation promotes epithelial-mesenchymal transition by inducing senescence escape in endometriosis

Endometrial epithelial cells carry distinct cancer-associated alterations that may be more susceptible to endometriosis. Mouse models have shown that overexpression of SIRT1 associated with oncogene activation contributes to the pathogenesis of endometriosis, but the underlying reason remains elusive. Here, we used integrated systems biology analysis and found that enrichment of endometrial stromal fibroblasts in endometriosis and their cellular abundance correlated negatively with epithelial cells in clinical specimens. Furthermore, endometrial epithelial cells were characterized by significant overexpression of SIRT1, which is involved in triggering the EMT switch by escaping damage or oncogene-induced induced senescence in clinical specimens and in vitro human cell line models. This observation supports that genetic and epigenetic incident favors endometrial epithelia cells escape from senescence and fuel EMT process in endometriosis, what could be overcome by downregulation of SIRT1.

Automated summary

This study found that the quantity of endometrial epithelial cells and stromal fibroblasts in endometriosis is correlated with the expression level of SIRT1. Overexpression of SIRT1 in endometrial epithelial cells triggers the EMT process, allowing them to escape senescence induced by damage or oncogenes. This observation supports the hypothesis that genetic and epigenetic factors help endometrial epithelial cells evade senescence and promote the EMT process in endometriosis.