title: MicroRNA-126 regulates HOXA9 by binding to the homeobox.
abstract: The PicTar program predicted that microRNA-126 (miR-126), miR-145, and let-7s target highly conserved sites within the Hoxa9 homeobox. There are increased nucleotide constraints in the three microRNA seed sites among Hoxa9 genes beyond that required to maintain protein identity, suggesting additional functional conservation. In preliminary experiments, forced expression of these microRNAs in Hoxa9-immortalized bone marrow cells downregulated the HOXA9 protein and caused loss of biological activity. The microRNAs were shown to target their predicted sites within the homeobox. miR-126 and Hoxa9 mRNA are coexpressed in hematopoietic stem cells and downregulated in parallel during progenitor cell differentiation; however, miR-145 is barely detectable in hematopoietic cells, and let-7s are highly expressed in bone marrow progenitors, suggesting that miR-126 may function in normal hematopoietic cells to modulate HOXA9 protein. In support of this hypothesis, expression of miR-126 alone in MLL-ENL-immortalized bone marrow cells decreased endogenous HOXA9 protein, while inhibition of endogenous miR-126 increased expression of HOXA9 in F9 cells.
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA. wfshen@itsa.ucsf.edu
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Shen
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Hu
authors.forename: Lalita
authors.initials: L
authors.lastname: Uttarwar
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Passegue
authors.forename: Corey
authors.initials: C
authors.lastname: Largman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D015536:Down-Regulation; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D018398:Homeodomain Proteins; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; C097899:homeobox protein HOXA9