MBE Advance Access published online on July 29, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn165
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Research Article |
MiR-150 negatively regulates c-Myb expression, which is evolutionarily conserved and plays an important role in developmental process
1 Genomics Research Center, Academia Sinica, 128, Academia Road, Sec. 2, Taipei 115, Taiwan
2 Institute of Cellular and Organismic Biology, Academia Sinica, 128, Academia Road, Sec. 2, Taipei 115, Taiwan
3 Department of Pediatrics/Hematology-Oncology, University of California San Diego Medical Center, 200 W. Arbor Drive, San Diego, CA 92103-8447, USA
Corresponding author Dr AL Yu, Genomics Research Center, Academia Sinica, 128, Academia Road, Sec. 2, Nankang Dist., Taipei 115, Taiwan. E-mail: aliceyu{at}ucsd.edu. Phone: +886-2-2789-9930. Fax: +886-2-2789-9931
Received for publication April 10, 2008. Revision received July 9, 2008. Accepted for publication July 23, 2008.
Human c-Myb proto-oncogene is highly expressed in hematopoietic progenitors as well as leukemia and certain solid tumor. However, the regulatory mechanisms of its expression and biological functions remain largely unclear. Recently, c-Myb has been shown to be targeted by microRNA-150 (miR-150) which thereby controls B cell differentiation in mice. In this study, we demonstrated that c-Myb is an evolutionarily conserved target of miR-150 in human and zebrafish, using reporter assays. Ectopic expression of miR-150 in breast cancer and leukemic cells repressed endogenous c-Myb at both mRNA and protein levels. Among several leukemia cell lines, primary leukemia cells, and normal lymphocytes, expression levels of miR-150 inversely correlated with c-Myb. MiR-150 over-expression or c-Myb silencing in zebrafish zygotes led to similar and serious phenotypic defects in zebrafish, and the phenotypic aberrations induced by miR-150 could be reversed by co-injection of c-Myb mRNA. Our findings suggest that c-Myb is an evolutionally conserved target of miR-150 and miR-150/c-Myb interaction is important for embryonic development and possibly oncogenesis.
Key Words: microRNA miR-150 c-Myb
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