METTL14 promotes the migration and invasion of breast cancer cells by modulating N6methyladenosine and hsamiR146a5p expression.
Oncol Rep
; 43(5): 1375-1386, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32323801
ABSTRACT
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancerrelated death among women worldwide. Evidence indicates that posttranscriptional N6methyladenosine (m6A) modification modulates BC development. In the present study, we assessed BC and normal tissues to investigate this connection. RNA m6A levels were determined by methylation quantification assay. The effects of methyltransferaselike 14 (METTL14) gainofexpression or cotransfection with an m6A inhibitor on cell migration and invasion abilities were determined by Transwell assays. The levels of differentially expressed (DE) miRNAs were verified by realtime quantitative PCR (RTqPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were performed to analyze potential function of target genes of the DE miRNAs. The effects of candidate miRNAs modulated by METTL14 on cell migration and invasion abilities were confirmed by Transwell assays. We demonstrated that m6A methyltransferase METTL14 was significantly upregulated in BC tissues compared with normal tissues. METTL14 gain and lossofexpression regulated m6A levels in MCF7 and MDAMB231 cells. The cell function assays revealed that METTL14 overexpression enhanced the migration and invasion capacities of BC cells. Moreover, treatment with the m6A inhibitor suppressed this enhanced cell migration and invasion. Additionally, aberrant expression of METTL14 reshaped the miRNA profile in BC cell lines. The remodeled DE miRNA/mRNA network was found to be most enriched in cancer pathways, and DE miRNAs were enriched in cell adhesion terms. hsamiR146a5p modulated by METTL14 promoted cell migration and invasion. METTL14 modulates m6A modification and hsamiR146a5p expression, thereby affecting the migration and invasion of breast cancer cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Adenosina
/
Regulação para Cima
/
MicroRNAs
/
Metiltransferases
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article