Home LiteratureArticle Details
PMID: 19850741 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

MicroRNA 29b functions in acute myeloid leukemia.

Blood ·Vol. 114 ·No. 26 ·2009-12-17 ·Pages 5331-41

Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, Zanesi N, Kornblau SM, Marcucci G, Calin GA, Andreeff M, Croce CM

Abstract

MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of acute myelogeneous leukemia (AML), but their impact on AML pathogenesis is poorly understood. We have previously shown that miR-29b expression is deregulated in primary AML blasts. In this work, we investigated the functional role of miR-29b in leukemogenesis. Restoration of miR-29b in AML cell lines and primary samples induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia model. Transcriptome analysis after ectopic transfection of synthetic miR-29b into leukemia cells indicates that miR-29b target apoptosis, cell cycle, and proliferation pathways. A significant enrichment for apoptosis genes, including MCL-1, was found among the mRNAs inversely correlated with miR-29b expression in 45 primary AML samples. Together, the data support a tumor suppressor role for miR-29 and provide a rationale for the use of synthetic miR-29b oligonucleotides as a novel strategy to improve treatment response in AML.

MeSH Terms
Animals Apoptosis/genetics Blotting, Northern Blotting, Western Cell Proliferation Female Gene Expression Gene Expression Regulation, Leukemic Humans Leukemia, Myeloid, Acute/genetics Mice Mice, Nude MicroRNAs/genetics Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Transfection Xenograft Model Antitumor Assays
Chemicals
MIRN29a microRNA, human MicroRNAs
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Garzon Ramiro
Division of Hematology and Oncology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Heaphy Catherine E A
Havelange Violaine
Fabbri Muller
Volinia Stefano
Tsao Twee
Zanesi Nicola
Kornblau Steven M
Marcucci Guido
Calin George A
Andreeff Michael
Croce Carlo M
References (38)
38 references, click to expand
  1. MicroRNA gene expression deregulation in human breast cancer.
    Cancer Res. 2005 Aug 15;65(16):7065-70 PMID: 16103053
  2. Identification of a gene expression signature associated with pediatric AML prognosis.
    Blood. 2003 Sep 1;102(5):1849-56 PMID: 12738660
  3. MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia.
    Blood. 2008 Mar 15;111(6):3183-9 PMID: 18187662
  4. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1.
    Cell. 1999 Sep 17;98(6):859-69 PMID: 10499802
  5. Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction.
    EMBO J. 2007 May 2;26(9):2361-70 PMID: 17431401
  6. A hexanucleotide element directs microRNA nuclear import.
    Science. 2007 Jan 5;315(5808):97-100 PMID: 17204650
  7. A pancreatic islet-specific microRNA regulates insulin secretion.
    Nature. 2004 Nov 11;432(7014):226-30 PMID: 15538371
  8. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia.
    Blood. 2008 May 15;111(10):5078-85 PMID: 18337557
  9. Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases.
    Blood. 1996 Sep 15;88(6):1930-5 PMID: 8822909
  10. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?
    Blood. 2007 Jan 15;109(2):431-48 PMID: 16960150
  11. MicroRNA expression and function in cancer.
    Trends Mol Med. 2006 Dec;12(12):580-7 PMID: 17071139
  12. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3945-50 PMID: 18308931
  13. Bim is a suppressor of Myc-induced mouse B cell leukemia.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6164-9 PMID: 15079075
  14. Combinatorial microRNA target predictions.
    Nat Genet. 2005 May;37(5):495-500 PMID: 15806104
  15. Functional proteomic profiling of AML predicts response and survival.
    Blood. 2009 Jan 1;113(1):154-64 PMID: 18840713
  16. MicroRNAs in vertebrate development.
    Curr Opin Genet Dev. 2005 Aug;15(4):410-5 PMID: 15979303
  17. Acute myeloid leukemia.
    N Engl J Med. 1999 Sep 30;341(14):1051-62 PMID: 10502596
  18. miR-15 and miR-16 induce apoptosis by targeting BCL2.
    Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9 PMID: 16166262
  19. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
    Nature. 2005 Feb 17;433(7027):769-73 PMID: 15685193
  20. BH3-Only proteins-essential initiators of apoptotic cell death.
    Cell. 2000 Dec 8;103(6):839-42 PMID: 11136969
  21. Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse.
    Blood. 1998 Feb 1;91(3):991-1000 PMID: 9446661
  22. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.
    Cancer Cell. 2006 Mar;9(3):189-98 PMID: 16530703
  23. MicroRNAs and cell cycle regulation.
    Cell Cycle. 2007 Sep 1;6(17):2127-32 PMID: 17786041
  24. DAVID: Database for Annotation, Visualization, and Integrated Discovery.
    Genome Biol. 2003;4(5):P3 PMID: 12734009
  25. Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity.
    Mol Cancer Ther. 2004 Feb;3(2):103-10 PMID: 14985450
  26. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.
    N Engl J Med. 2005 Oct 27;353(17):1793-801 PMID: 16251535
  27. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23).
    Leukemia. 2003 Mar;17(3):637-41 PMID: 12646957
  28. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B.
    Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15805-10 PMID: 17890317
  29. Real-time quantification of microRNAs by stem-loop RT-PCR.
    Nucleic Acids Res. 2005 Nov 27;33(20):e179 PMID: 16314309
  30. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  31. Unique biology of Mcl-1: therapeutic opportunities in cancer.
    Curr Mol Med. 2008 Mar;8(2):138-47 PMID: 18336294
  32. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  33. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
    Methods. 2001 Dec;25(4):402-8 PMID: 11846609
  34. NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma.
    Cancer Cell. 2008 Nov 4;14(5):369-81 PMID: 18977326
  35. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis.
    Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13027-32 PMID: 18723672
  36. mir-29 regulates Mcl-1 protein expression and apoptosis.
    Oncogene. 2007 Sep 13;26(42):6133-40 PMID: 17404574
  37. MiR-15a and miR-16-1 cluster functions in human leukemia.
    Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166-71 PMID: 18362358
  38. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2009-03-211938
Published
2009-12-17
Epub
2009-00-22
Pages
5331-41
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2796138
Subset
IM
Grants
NCI NIH HHS · P01 CA055164 · United States
NCI NIH HHS · P01CA055164 · United States
External Links
PubMed source DOI: 10.1182/blood-2009-03-211938 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2