Epigenetically altered miR?193a?3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7.
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ABSTRACT: 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 downregulated 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.
SUBMITTER: Tang Y
PROVIDER: S-EPMC6488183 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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