title: GPER mediated estradiol reduces miR-148a to promote HLA-G expression in breast cancer.
abstract: Breast cancer is the most common malignant diseases in women. miR-148a plays an important role in regulation of cancer cell proliferation and cancer invasion and down-regulation of miR-148a has been reported in both estrogen receptor (ER) positive and triple-negative (TN) breast cancer. However, the regulation mechanism of miR-148a is unclear. The role of estrogen signaling, a signaling pathway is important in development and progression of breast cancer. Therefore, we speculated that E2 may regulate miR-148a through G-protein-coupled estrogen receptor-1 (GPER). To test our hypothesis, we checked the effects of E2 on miR-148a expression in ER positive breast cancer cell MCF-7 and TN cancer cell MDA-MB-231. Then we used GPER inhibitor G15 to investigate whether GPER is involved in regulation of E2 on miR-148a. Furthermore, we analyzed whether E2 affects the expression of HLA-G, which is a miR-148a target gene through GPER. The results showed that E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells, GPER mediates the E2-induced increase in miR-148a expression in MCF-7 and MDA-MB-231 cells and E2-GPER regulates the expression of HLA-G by miR-148a. In conclusion, our findings offer important new insights into the ability of estrogenic GPER signaling to trigger HLA-G expression through inhibiting miR-148a that supports immune evasion in breast cancer.
authors: Department of Surgical Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: taosifeng@aliyun.com.
authors: Sifeng
authors: S
authors: Tao
authors: Department of Surgical Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Haifei
authors: H
authors: He
authors: Department of Surgical Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Qiang
authors: Q
authors: Chen
authors: Department of Surgical Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Wenjie
authors: W
authors: Yue
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C109584:GPER1 protein, human; D059951:HLA-G Antigens; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol
keywords: Breast cancer; Estrogen; G-protein-coupled estrogen receptor-1; HLA-G; miR-148a