Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing.
Proc Natl Acad Sci U S A
; 108(11): 4394-9, 2011 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-21368194
ABSTRACT
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the posttranscriptional level and are critical for many cellular pathways. The disruption of miRNAs and their processing machineries also contributes to the development of human tumors. A common scenario for miRNA expression in carcinogenesis is emerging that shows that impaired miRNA production and/or down-regulation of these transcripts occurs in many neoplasms. Several of these lost miRNAs have tumor-suppressor features, so strategies to restore their expression globally in malignancies would be a welcome addition to the current therapeutic arsenal against cancer. Herein, we show that the small molecule enoxacin, a fluoroquinolone used as an antibacterial compound, enhances the production of miRNAs with tumor suppressor functions by binding to the miRNA biosynthesis protein TAR RNA-binding protein 2 (TRBP). The use of enoxacin in human cell cultures and xenografted, orthotopic, and metastatic mouse models reveals a TRBP-dependent and cancer-specific growth-inhibitory effect of the drug. These results highlight the key role of disrupted miRNA expression patterns in tumorigenesis, and suggest a unique strategy for restoring the distorted microRNAome of cancer cells to a more physiological setting.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Enoxacino
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Processamento Pós-Transcricional do RNA
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Proteínas de Ligação a RNA
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MicroRNAs
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Bibliotecas de Moléculas Pequenas
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article