These authors contribute equally to this work.
A statin-regulated microRNA represses human c-Myc expression and function
Article first published online: 7 AUG 2012
Copyright © 2012 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 4, Issue 9, pages 896–909, September 2012
How to Cite
Takwi, A. A. L., Li, Y., Becker Buscaglia, L. E., Zhang, J., Choudhury, S., Park, A. K., Liu, M., Young, K. H., Park, W.-Y., Martin, R. C. G. and Li, Y. (2012), A statin-regulated microRNA represses human c-Myc expression and function. EMBO Mol Med, 4: 896–909. doi: 10.1002/emmm.201101045
- Issue published online: 4 SEP 2012
- Article first published online: 7 AUG 2012
- Manuscript Accepted: 6 JUN 2012
- Manuscript Revised: 4 JUN 2012
- Manuscript Received: 28 OCT 2011
- Funded Access
- NCI/NIH. Grant Number: R01 CA138688
- Center for Environmental Genomics and Integrated Biology. Grant Number: NIEHS/NIH; P30 ES014443
- Diabetes and Obesity Center. Grant Number: NCRR/NIH; P20 RR024489
c-Myc dysregulation is one of the most common abnormalities found in human cancer. MicroRNAs (miRNAs) are functionally intertwined with the c-Myc network as multiple miRNAs are regulated by c-Myc, while others directly suppress c-Myc expression. In this work, we identified miR-33b as a primate-specific negative regulator of c-Myc. The human miR-33b gene is located at 17p11.2, a genomic locus frequently lost in medulloblastomas, of which a subset displays c-Myc overproduction. Through a small-scale screening with drugs approved by the US Food and Drug Administration (FDA), we found that lovastatin upregulated miR-33b expression, reduced cell proliferation and impaired c-Myc expression and function in miR-33b-positive medulloblastoma cells. In addition, a low dose of lovastatin treatment at a level comparable to approved human oral use reduced tumour growth in mice orthotopically xenografted with cells carrying miR-33b, but not with cells lacking miR-33b. This work presents a highly promising therapeutic option, using drug repurposing and a miRNA as a biomarker, against cancers that overexpress c-Myc.