Activation of GPER by E2 promotes proliferation, invasion and migration of breast cancer cells by regulating the miR-124/CD151 pathway.

Abstract

Breast cancer is one of the most common malignancies worldwide and is responsible for a high mortality rate. However, the underlying pathological mechanism of breast cancer remains unclear. MicroRNAs (miRNAs/miRs) play critical roles in the progression of breast cancer. Recent studies have reported that miR-124/CD151 participates in the development of breast cancer. However, the exact molecular mechanism of miR-124/CD151 action in 17β-estradiol (E2)-treated breast cancer cells remains unknown. Thus, the present study aimed to investigate miR-124 and CD151 expression levels in MCF-7 cells treated with E2 via reverse transcription-quantitative PCR and western blot analyses. Bioinformatic analysis was performed to predict and identify whether CD151 is a potential target of miR-124. The Cell Counting Kit-8 and colony formation assays were performed to detect proliferation of MCF-7 cells. In addition, the invasive and migratory abilities of MCF-7 cells were assessed via the Transwell and wound healing assays, respectively. The results demonstrated that E2 downregulated miR-124 expression, while upregulating G protein -coupled estrogen receptor (GPER) expression in MCF-7 cells. Following treatment with the GPER antagonist, G15, miR-124 expression was significantly enhanced and E2-induced proliferation, invasion and migration of MCF-7 cells were notably inhibited. In addition, CD151 was confirmed as a direct target of miR-124. CD151 silencing remarkably suppressed the proliferation, invasion and migration of E2-induced MCF-7 cells. Taken together, these results suggest that upregulation of GPER expression induced by E2 promotes proliferation, invasion and migration of breast cancer cells by regulating the miR-124/CD151 pathway. Thus, the results of the present study provide a potential novel method for the treatment and prognosis of breast cancer.