c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development.
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.
Lin
You-Chin
YC
Genomics Research Center, Academia Sinica Taipei, Taiwan.
Kuo
Ming-Wei
MW
Yu
John
J
Kuo
Huan-Hsien
HH
Lin
Ruey-Jen
RJ
Lo
Wan-Lin
WL
Yu
Alice L
AL
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish
D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb