miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts.
Nucleic Acids Res
; 41(10): 5400-12, 2013 May 01.
Article
en En
| MEDLINE
| ID: mdl-23580553
ABSTRACT
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Citoesqueleto
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Neoplasias de la Mama
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Regulación Neoplásica de la Expresión Génica
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Movimiento Celular
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MicroARNs
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article