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

AAL Takwi, Y Li, LE Becker Buscaglia… - EMBO molecular …, 2012 - embopress.org
AAL Takwi, Y Li, LE Becker Buscaglia, J Zhang, S Choudhury, AK Park, M Liu, KH Young…
EMBO molecular medicine, 2012embopress.org
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 …
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.
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