HOXA9 regulates miR-155 in hematopoietic cells.
HOXA9-mediated up-regulation of miR-155 was noted during an array-based analysis of microRNA expression in Hoxa9(-/-)bone marrow (BM) cells. HOXA9 induction of miR-155 was confirmed in these samples, as well as in wild-type versus Hoxa9-deficient marrow, using northern analysis and qRT-PCR. Infection of wild-type BM with HOXA9 expressing or GFP(+) control virus further confirmed HOXA9-mediated regulation of miR-155. miR-155 expression paralleled Hoxa9 mRNA expression in fractionated BM progenitors, being highest in the stem cell enriched pools. HOXA9 capacity to induce myeloid colony formation was blunted in miR-155-deficient BM cells, indicating that miR-155 is a downstream mediator of HOXA9 function in blood cells. Pu.1, an important regulator of myelopoiesis, was identified as a putative down stream target for miR-155. Although miR-155 was shown to down-regulate the Pu.1 protein, HOXA9 did not appear to modulate Pu.1 expression in murine BM cells.
Hu
Yu-Long
YL
Department of Medicine, Department of Veterans Affairs Medical Center and University of California, San Francisco, CA 94143, USA.
Fong
Stephen
S
Largman
Corey
C
Shen
Wei-Fang
WF
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation; D000099232:Proto-Oncogene Protein Spi-1
D018398:Homeodomain Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C532623:Mirn155 microRNA, mouse; C097899:homeobox protein HOXA9
Mol Cancer Res. 2008 Dec;6(12):1830-40
19074828
Mol Cell Biol. 1997 Nov;17(11):6448-58
9343407
Curr Opin Genet Dev. 1998 Aug;8(4):423-9
9729718
Mol Cell Biol. 2000 May;20(9):3274-85
10757811
J Cell Biochem. 2008 Jun 1;104(3):805-17
18189265
Mol Cell Biol. 2008 Jul;28(14):4609-19
18474618
EMBO J. 2001 Feb 1;20(3):350-61
11157742
Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii50-5
19022814
Cell. 2003 Dec 26;115(7):787-98
14697198
Mol Cell Biol. 1999 Nov;19(11):7577-88
10523646
Genome Res. 2008 Nov;18(11):1787-97
18849523
Blood. 1997 Mar 15;89(6):1922-30
9058712
Immunity. 2007 Dec;27(6):847-59
18055230
J Biol Chem. 1997 Mar 28;272(13):8198-206
9079637
Biochem Soc Trans. 2008 Jun;36(Pt 3):531-3
18481999
Blood. 2009 Aug 13;114(7):1374-82
19520806
Semin Oncol. 2006 Apr;33(2):167-73
16616063
Leukemia. 2002 Feb;16(2):186-95
11840284
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627-32
15738415
Blood. 1998 Jul 15;92(2):383-93
9657735
Blood. 2007 Jun 1;109(11):4732-8
17327400
EMBO J. 1998 Jul 1;17(13):3714-25
9649441
Blood. 2004 Mar 1;103(5):1676-84
14604967
Circ Res. 2004 Apr 2;94(6):743-51
14764452
Leuk Lymphoma. 2009 Feb;50(2):160-70
19160125
Science. 2007 Apr 27;316(5824):604-8
17463289
Leukemia. 1999 Dec;13(12):1993-9
10602420
Genes Dev. 1995 Mar 15;9(6):663-74
7729685
J Biol Chem. 2005 Apr 1;280(13):12359-70
15681849
EMBO J. 1998 Mar 2;17(5):1434-45
9482740
Dev Biol. 1997 Jan 15;181(2):186-96
9013929
Mol Cell Biol. 1999 Apr;19(4):3051-61
10082572
Mol Cell Biol. 2009 Sep;29(18):5181-92
19620287
Development. 1996 Feb;122(2):461-72
8625797
Blood. 2005 Feb 15;105(4):1456-66
15522959
Blood. 2005 Dec 1;106(12):3988-94
16091451
Leukemia. 2009 Jul;23(7):1257-63
19148134
Int J Biochem Cell Biol. 2008;40(1):22-7
17374502
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):541-6
9892669
Nature. 2003 Oct 30;425(6961):926-33
14586461
Nat Med. 2005 May;11(5):531-7
15821746
Science. 2004 Jan 2;303(5654):83-6
14657504
Eur J Haematol. 2008 Oct;81(4):304-10
18573170
Cell. 2006 Jul 28;126(2):415-26
16873070
Science. 1999 Oct 15;286(5439):531-7
10521349
Genome Biol. 2005;6(8):R71
16086853
Exp Hematol. 2007 Apr;35(4):551-64
17379065
Blood. 1996 Aug 15;88(4):1234-47
8695841
Leukemia. 1999 May;13(5):687-98
10374871
Curr Opin Hematol. 2008 Jul;15(4):352-8
18536574
J Exp Med. 2008 Mar 17;205(3):585-94
18299402