Epigenetically altered miR193a3p promotes HER2 positive breast cancer aggressiveness by targeting GRB7.
Int J Mol Med
; 43(6): 2352-2360, 2019 Jun.
Article
em En
| MEDLINE
| ID: mdl-31017268
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 miR193a3p inhibiting the progress of HER2 positive breast cancer. The expression of miR193a3p was evaluated by quantitative polymerase chain reaction (PCR). The methylation status of miR193a3p was evaluated by PCR and pyrosequencing analysis. Overexpression of miR193a3p and growth factor receptor bound protein 7 (GRB7) combined with in vitro tumorigenic assays were conducted to determine the carcinostatic capacities of miR193a3p in HER2 positive breast cancer cells. The association between miR193a3p and GRB7 was determined by luciferase reporter assay. Protein level was evaluated using western blot analysis. miR193a3p was downregulated in HER2 positive breast cancer cells and clinical tissues. Methylationmediated silencing led to decreased expression of miR193a3p in HER2 positive breast cancer. Overexpression of miR193a3p could inhibit proliferation, migration and invasion of breast cancer cells. Overexpression of GRB7 could abolish this effect. miR193a3p could directly target the 3' untranslated region of GRB7. miR193a3p could directly or indirectly target extracellular signalregulated kinase 1/2 (ERK1/2) and forkhead box M1 (FOXM1) signaling. In conclusion, it was identified that silencing of miR193a3p through hypermethylation can promote HER2 positive breast cancer progress by targeting GRB7, ERK1/2 and FOXM1 signaling. The function of miR193a3p in HER2 positive breast cancer implicates its potential application in therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Receptor ErbB-2
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MicroRNAs
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Proteína Adaptadora GRB7
/
Invasividade Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Int J Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de publicação:
GR
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GRECIA
/
GREECE
/
GRÉCIA