Epigenetically altered miR-193a-3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7

被引:19
|
作者
Tang, Yiyin [1 ]
Yang, Siyuan [1 ]
Wang, Maohua [1 ]
Liu, Dequan [1 ]
Liu, Yang [1 ]
Zhang, Ying [1 ]
Zhang, Qian [1 ]
机构
[1] Kunming Med Univ, Tumor Hosp Yunnan Prov, Affiliated Hosp 3, Dept Mammary Surg 1, Kunming 650118, Yunnan, Peoples R China
关键词
breast cancer; human epidermal growth factor receptor 2; microRNA-193a-3p; growth factor receptor bound protein 7; OVARIAN-CANCER; TUMOR-SUPPRESSOR; LUNG-CANCER; GROWTH; EXPRESSION; RESISTANCE; OVEREXPRESSION; ACTIVATION; MICRORNA; SURVIVAL;
D O I
10.3892/ijmm.2019.4167
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Emerging evidence has demonstrated that microRNAs (miRNAs/miRs) have various biological functions in the development of human epidermal growth factor receptor 2 (HER2) positive breast cancer. The aim of the present study is to reveal the mechanism of miR-193a-3p inhibiting the progress of HER2 positive breast cancer. The expression of miR-193a-3p was evaluated by quantitative polymerase chain reaction (PCR). The methylation status of miR-193a-3p was evaluated by PCR and pyrosequencing analysis. Overexpression of miR-193a-3p and growth factor receptor bound protein 7 (GRB7) combined with in vitro tumorigenic assays were conducted to determine the carcinostatic capacities of miR-193a-3p in HER2 positive breast cancer cells. The association between miR-193a-3p and GRB7 was determined by luciferase reporter assay. Protein level was evaluated using western blot analysis. miR-193a-3p was down-regulated in HER2 positive breast cancer cells and clinical tissues. Methylation-mediated silencing led to decreased expression of miR-193a-3p in HER2 positive breast cancer. Overexpression of miR-193a-3p could inhibit proliferation, migration and invasion of breast cancer cells. Overexpression of GRB7 could abolish this effect. miR-193a-3p could directly target the 3 untranslated region of GRB7. miR-193a-3p could directly or indirectly target extracellular signal-regulated kinase 1/2 (ERK1/2) and forkhead box M1 (FOXM1) signaling. In conclusion, it was identified that silencing of miR-193a-3p through hypermethylation can promote HER2 positive breast cancer progress by targeting GRB7, ERK1/2 and FOXM1 signaling. The function of miR-193a-3p in HER2 positive breast cancer implicates its potential application in therapy.
引用
收藏
页码:2352 / 2360
页数:9
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