Post-transcriptional Regulation of MMP16 and TIMP2 Expression via miR-382, miR-410 and miR-200b in Endometrial Cancer.
Cancer Genomics Proteomics
; 14(5): 389-401, 2017.
Article
em En
| MEDLINE
| ID: mdl-28871006
ABSTRACT
BACKGROUND/AIM:
The post-transcriptional regulation of matrix metalloproteinases (MMPs) via microRNAs (miRNAs) has been recently described in numerous human malignancies. However, the exact mechanisms of miRNA-mediated MMPs deregulation in endometrial cancer (EC) remain unclear. Herein, we aimed to analyze the expression of MMP2, MMP16 and TIMP2 and identify miRNAs that modulate their expression. MATERIALS ANDMETHODS:
Protein expression was assessed by immunohistochemistry in formalin-fixed paraffin-embedded EC samples. Target prediction algorithms were applied to select miRNAs binding the 3'UTRs of MMP16 (miR-377, miR-382, miR-410, miR-200b) or TIMP2 (miR-200b), and their levels were measured by qPCR in laser capture-microdissected tissue fragments. Luciferase assays and western blotting were used to indicate individual miRNA- mRNA interactions.RESULTS:
Overexpression of MMP2 and MMP16 in cancerous tissues corresponded to down-regulation of miR-377, miR-382 and miR-410, while decreased expression of TIMP2 was associated with miR-200b up-regulation. In vitro experiments confirmed direct regulation of MMP16 by miR-382 and miR-410, and TIMP2 by miR-200b in EC Ishikawa cells.CONCLUSION:
We demonstrated novel mechanisms of miRNA-mediated regulation of MMPs activity in EC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Regulação Neoplásica da Expressão Gênica
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Neoplasias do Endométrio
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Inibidor Tecidual de Metaloproteinase-2
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MicroRNAs
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Metaloproteinase 16 da Matriz
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article