title: c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development.
abstract: 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.
authors.affiliation: Genomics Research Center, Academia Sinica Taipei, Taiwan.
authors.forename: You-Chin
authors.initials: YC
authors.lastname: Lin
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Kuo
authors.forename: John
authors.initials: J
authors.lastname: Yu
authors.forename: Huan-Hsien
authors.initials: HH
authors.lastname: Kuo
authors.forename: Ruey-Jen
authors.initials: RJ
authors.lastname: Lin
authors.forename: Wan-Lin
authors.initials: WL
authors.lastname: Lo
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
mesh_terms: 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
chemical_list: D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb