G protein-coupled estrogen receptor/miR-148a/human leukocyte antigen-G signaling pathway mediates cell apoptosis of ovarian endometriosis

The focus of the current study was a G protein-coupled estrogen receptor (GPER)/microRNA (miR)-148a/human leukocyte antigen-G (HLA-G) signaling pathway in ovarian endometriosis. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the changes in miR-148a expression. A MTT assay, flow cytometry and caspase-3/9 activity assays were performed to analyze cell proliferation, apoptosis and caspase-3/9 activity levels, respectively. Protein expression was measured using western blot analysis. In tissue samples from healthy controls, and patients with endometriosis and endometriosis-associated ovarian cancer, the expression of miR-148a was lower in in endometriosis and EAOC samples compared with healthy controls. Overexpression of miR-148a using miR mimics significantly decreased proliferation, promoted apoptosis, increased the Bcl-2 associated X apoptosis regulator (Bax)/Bcl-2 apoptosis regulator (Bcl-2) ratio and caspase3/9 activity, and suppressed HLA-G protein expression in Hs 832(C).T cells. miR-148a downregulation using miR inhibitor significantly increased cell viability, inhibited apoptosis, and reduced the Bax/Bcl-2 ratio and caspase3/9 activity, and induced HLA-G protein expression in Hs 832(C).T cells. The GPER inhibitor, G15, suppressed GPER protein expression, upregulated miR-148a expression, decreased cell proliferation, promoted apoptosis, increased the Bax/Bcl-2 ratio and caspase3 activity, and suppressed HLA-G protein expression in Hs 832(C).T cells. The findings indicate that GPERImiR-148a/HLA-G signaling pathway may mediates the development of ovarian endometriosis and may become a potential therapeutic target for the treatment of endometriosis.