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

EMBO Molecular Medicine

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 】

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.

【 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.