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

Abstract

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 GPER/miR‑148a/HLA‑G signaling pathway may mediates the development of ovarian endometriosis and may become a potential therapeutic target for the treatment of endometriosis.

Estrogen Promotes cAMP Production in Mesenchymal Stem Cells by Regulating ADCY2

“…The expression of miR-152 is increased in the placental tissues and serum of PE, and this increased miR-152 expression can promote the apoptosis of trophoblast cells (32,33). Furthermore, miR-148a could modulate differentiation of MSCs (34), and the expression and function of miR-148a /152 were associated with estrogen signaling pathway (35)(36)(37)(38). All these findings suggest that miR-148a and miR-152 are key molecules mediating the function of E2 in MSCs.…”

Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis

“…Abbreviations miRNA: microRNA; RISC: RNA-induced silencing complex; PDGF: Plateletderived growth factor; TGF: Transforming growth factor; PCD: Programmed [97] miR-503 Down-regulated Targeting BCL-2 mRNAs Treatment and biomarker [98] miR-183 Down-regulated Reducing apoptosis Treatment and biomarker [99] miR-29c Down-regulated Targeting c-JUN (a protein which regulates gene expression) Treatment and biomarker [100] miR-148a -Affecting BCL-2 expression and caspase-3/9 through G protein coupled estrogen receptor/miR148a/human leukocyte antigen G signaling pathway Treatment [101] miR-210 Up-regulated Inhibition of apoptosis by targeting signal transducer and activator of transcription 3…”

Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation

“…In addition, HLA-G was expressed in both in situ and ectopic endometria of patients with adenomyosis, and HLA-G expression was also detected in ectopic endometrial lesions during menstruation. The findings suggest that epithelial cells carrying HLA-G may enter the peritoneal cavity during retrograde menstruation, allowing a local reaction of antigen with KIR2DL4 and mediating immune escape ( 168 – 170 ). A retrospective study showed that polymorphisms in HLA-G , LILRB1 , and LILRB2 genes contributed to the susceptibility and severity of endometriosis, but not KIR2DL4 polymorphisms ( 171 ).…”