Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Melo, S (Author) Other; Villanueva, A (Author) Other; Moutinho, C (Author) Other; Davalos, V (Author) Other; Spizzo, R (Author) Other; Ivan, C (Author) Other; Rossi, S (Author) Other; Setien, F (Author) Other; Casanovas, O (Author) Other; Simo Riudalbas, L (Author) Other; Carmona, J (Author) Other; Carrere, J (Author) Other; Vidal, A (Author) Other; Aytes, A (Author) Other; Puertas, S (Author) Other; Ropero, S (Author) Other; Kalluri, R (Author) Other; Croce, CM (Author) Other; Calinc, GA (Author) Other; Esteller, M (Author) Other

Journal

Title: Proceedings of the National Academy of Sciences of the United States of America

Vol. 108

Pages: 4394-4399

ISSN: 0027-8424

Publisher: National Academy of Sciences

Indexing

Scopus - 181 Citations

Other information

Authenticus ID: P-009-FJE

DOI: 10.1073/pnas.1014720108

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific