Open AccessA statin‐regulated microRNA represses human c‐Myc expression and function
Author(s) -
Takwi Apana A. L.,
Li Yan,
Becker Buscaglia Lindsey E.,
Zhang Jingwen,
Choudhury Saibyasachi,
Park Ae Kyung,
Liu Mofang,
Young Ken H.,
Park WoongYang,
Martin Robert C. G.,
Li Yong
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201101045
Subject(s) - microrna , cancer research , gene knockdown , downregulation and upregulation , biology , regulator , cell growth , gene , genetics
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.