EMBO Molecular Medicine | |
A statin‐regulated microRNA represses human c‐Myc expression and function | |
Apana A. L. Takwi7  Yan Li5  Lindsey E. Becker Buscaglia7  Jingwen Zhang3  Saibyasachi Choudhury7  Ae Kyung Park6  Mofang Liu2  Ken H. Young4  Woong-Yang Park1  Robert C. G. Martin5  | |
[1] Department of Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Korea;State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, USA;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Division of Surgical Oncology, Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, USA;Department of Pharmacy, Sunchon National University College of Pharmacy, Sunchon, Korea;Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, Louisville, KY, USA | |
关键词: c‐Myc; lovastatin; medulloblastoma; microRNA; miR‐33b; | |
DOI : 10.1002/emmm.201101045 | |
来源: Wiley | |
【 摘 要 】
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.Abstract
【 授权许可】
CC BY
Copyright © 2012 EMBO Molecular Medicine
Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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