Referencia

Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4394-9

Autores

Melo S, Villanueva A, Moutinho C, Davalos V, Spizzo R, Ivan C, Rossi S, Setien F, Casanovas O, Simo-Riudalbas L, Carmona J, Carrere J, Vidal A, Aytes A, Puertas S, Ropero S, Kalluri R, Croce CM, Calin GA, Esteller M.

Resumen

Los microARNs son pequeñas moléculas reguladoras de los ARN mensajeros de muchos genes. Además de jugar un papel esencial en la biología celular y del desarrollo, la actividad de los mismos se encuentra alterada en patología humana como es el caso del cáncer. En los tumores existe un problema común de falta de producción de microARNs maduros con función inhibidora del crecimiento de la celula transformada. El artículo identifica un compuesto capaz de activar estos microARNs supresores de tumores y que posee actividad anticancerosa in vitro e in vivo.

Descripción

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.

Imágen artículo Mayo

REFERENCIA DEL GRUPO E INVESTIGADOR
El grupo del Dr Manel Esteller, Director del Programa de Epigenética y Biología del Cáncer (PEBC) del Instituto de Investigación Biomédica de Bellvitge (IDIBELL) e Investigador ICREA, está centrado en el estudio de los mecanismos epigenéticos implicados en patología humana, principalmente en el área del cancer. Sus trabajos han contribuido al conocimiento de los patrones alterados de metilación del DNA, modificación de histonas y producción de ARN no codificantes presentes en las células trasnformadas.

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