A statin‐regulated microRNA represses human c‐Myc expression and function
説明
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>miR‐33b</jats:italic> 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 <jats:italic>miR‐33b</jats:italic>, but not with cells lacking <jats:italic>miR‐33b</jats:italic>. This work presents a highly promising therapeutic option, using drug repurposing and a miRNA as a biomarker, against cancers that overexpress c‐Myc.</jats:p>
収録刊行物
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- EMBO Molecular Medicine
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EMBO Molecular Medicine 4 (9), 896-909, 2012-08-07
Springer Science and Business Media LLC