A statin-regulated microRNA represses human c-Myc expression and function

Abstract

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. © 2012 EMBO Molecular Medicine.