MEIS1-mediated Apoptosis via TNFR1 in Endometriosis.

Abstract

Abnormal apoptosis both maintains endometrial cell growth and induces endometrial pathogenesis. The etiology of endometriosis is unclear and no treatment is curative. Therefore, the aim herein was to identify genes involved in the pathogenesis of endometriosis. Using the data from our previous results and RNA sequencing data of normal endometrial tissue and ovarian endometrioma (OMA) tissue, along with Gene Expression Omnibus (GEO) dataset on endometriosis, we identified an apoptotic-related gene, meis homeobox I (MEIS1). Normal endometrium, eutopic endometrium and ectopic endometriotic tissues were used to detect MEIS1. Primary normal endometrial and eutopic endometrial stromal cells were isolated and cultured for exploring the function of MEIS1 and related pathways. A mouse endometriosis model was used to verify the therapeutic effects of MEIS1. The mRNA and protein of MEIS1 in tissues from patients with endometriosis were decreased. Overexpression of MEIS1 induced the apoptosis of primary eutopic endometrium stromal cells by regulating TNFR1. Using Cell Counting Kit 8 (CCK8) assay and EdU assay, we found that knockdown of MEIS1 promoted the proliferation of primary normal endometrium stromal cells. We also observe that upregulated MEIS1 may lead to caspase pathway activation, promoting endometrial cell apoptosis. Furthermore, MEIS1 lentivirus inhibited endometriotic lesion formation and induced apoptosis in the mouse endometriosis model. These cumulative findings suggest that MEIS1 may mediate apoptosis by initiating TNFR1 in endometrial cells via the caspase pathway.