miR-639 Expression Is Silenced by DNMT3A-Mediated Hypermethylation and Functions as a Tumor Suppressor in Liver Cancer Cells.
Mol Ther
; 28(2): 587-598, 2020 02 05.
Article
em En
| MEDLINE
| ID: mdl-31843451
ABSTRACT
Emerging evidence has indicated that abnormal methylation of DNA contributes to hepatocarcinogenesis. However, the regulatory mechanisms are not well known. Here, we revealed that microRNA-639 (miR-639) expression is downregulated in liver cancer tissues and cells. The repression of miR-639 expression was attributed to hypermethylation in its promoter region, and DNA methyltransferase (DNMT3A) was found to mediate this hypermethylation. Repression of miR-639 expression promoted cell growth and migration/invasion in vitro and the growth of tumors in xenograft mouse models. Furthermore, miR-639 bound to the 3' UTR of both MYST2 and ZEB1 and suppressed their expression. MYST2 promoted the growth of liver cancer cells and ZEB1 facilitated the migration/invasion of liver cancer cells. Ectopic expression of MYST2 and ZEB1 counteracted the repression of malignancy induced by miR-639, which coincided with the reciprocal correlation between miR-639 and MYST2 and ZEB1 expression in clinical hepatocellular carcinoma (HCC) tissues. Thus, DNMT3A-mediated hypermethylation suppressed miR-639 expression, derepressing the expression of MSYT2 and ZEB1, which promoted tumorigenesis of liver cancer. These findings may shed light on the mechanism of abnormal expression of miRNAs involved in the malignancy of liver cancer and provide new biomarkers for liver cancer.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Genes Supressores de Tumor
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Metilação de DNA
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Inativação Gênica
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MicroRNAs
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Interferência de RNA
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DNA (Citosina-5-)-Metiltransferases
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article