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MBE Advance Access originally published online on July 29, 2008
Molecular Biology and Evolution 2008 25(10):2189-2198; doi:10.1093/molbev/msn165
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

c-Myb Is an Evolutionary Conserved miR-150 Target and miR-150/c-Myb Interaction Is Important for Embryonic Development

You-Chin Lin*, Ming-Wei Kuo{dagger}, John Yu*,{dagger}, Huan-Hsien Kuo*, Ruey-Jen Lin*, Wan-Lin Lo* and Alice L. Yu*,{ddagger}

* Genomics Research Center, Academia Sinica Taipei, Taiwan
{dagger} Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
{ddagger} Department of Pediatrics/Hematology-Oncology, University of California San Diego Medical Center, San Diego

E-mail: aliceyu{at}ucsd.edu.

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 evolutionary 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 messenger RNA (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. The miR-150 overexpression 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 coinjection 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


Takashi Gojobori, Associate Editor


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