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

He,Shun  Zhi; Li,Jing; Bao,Hong  Chu; Wang,Mei  Mei; Wang,Xin  Rong; Huang,Xin; Li,Feng  Hua; Zhang,Wei; Xu,An  Li; Fang,Hao  Cui; Sheng,Yang  Xing

doi:10.3892/mmr.2018.9039

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

Authors:
- Shun Zhi He
- Jing Li
- Hong Chu Bao
- Mei Mei Wang
- Xin Rong Wang
- Xin Huang
- Feng Hua Li
- Wei Zhang
- An Li Xu
- Hao Cui Fang
- Yang Xing Sheng
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Affiliations: Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Electrocardiogram Room, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Reproductive Medicine Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Department of Gynecology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
Published online on: May 21, 2018 https://doi.org/10.3892/mmr.2018.9039
Pages: 1141-1148

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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.

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