Home LiteratureArticle Details
PMID: 19633662 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MicroRNA MiR-17 retards tissue growth and represses fibronectin expression.

Nature cell biology ·Vol. 11 ·No. 8 ·2009-08-00 ·Pages 1031-8

Shan SW, Lee DY, Deng Z, Shatseva T, Jeyapalan Z, Du WW, Zhang Y, Xuan JW, Yee SP, Siragam V, Yang BB

Abstract

MicroRNAs (miRNAs) are single-stranded regulatory RNAs, frequently expressed as clusters. Previous studies have demonstrated that the six-miRNA cluster miR-17~92 has important roles in tissue development and cancers. However, the precise role of each miRNA in the cluster is unknown. Here we show that overexpression of miR-17 results in decreased cell adhesion, migration and proliferation. Transgenic mice overexpressing miR-17 showed overall growth retardation, smaller organs and greatly reduced haematopoietic cell lineages. We found that fibronectin and the fibronectin type-III domain containing 3A (FNDC3A) are two targets that have their expression repressed by miR-17, both in vitro and in transgenic mice. Several lines of evidence support the notion that miR-17 causes cellular defects through its repression of fibronectin expression. Our single miRNA expression assay may be evolved to allow the manipulation of individual miRNA functions in vitro and in vivo. We anticipate that this could serve as a model for studying gene regulation by miRNAs in the development of gene therapy.

MeSH Terms
Animals Base Sequence Cell Adhesion Cell Line Cell Line, Tumor Cell Proliferation Female Fibronectins/genetics Flow Cytometry Gene Expression Regulation Humans Kidney/metabolism,pathology Liver/metabolism,pathology Male Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Transgenic MicroRNAs/genetics Molecular Sequence Data Myocardium/metabolism,pathology Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Nucleic Acid Spleen/metabolism,pathology Transfection
Chemicals
Fibronectins MIRN17 microRNA, human MicroRNAs Mirn17 microRNA, mouse
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Shan Sze Wan
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada.
Lee Daniel Y
Deng Zhaoqun
Shatseva Tatiana
Jeyapalan Zina
Du William W
Zhang Yaou
Xuan Jim W
Yee Siu-Pok
Siragam Vinayakumar
Yang Burton B
References (38)
38 references, click to expand
  1. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage.
    Cell. 2008 Mar 7;132(5):860-74 PMID: 18329371
  2. The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation.
    Nat Cell Biol. 2006 Mar;8(3):278-84 PMID: 16489342
  3. A microRNA polycistron as a potential human oncogene.
    Nature. 2005 Jun 9;435(7043):828-33 PMID: 15944707
  4. The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA-mediated gene regulation.
    PLoS One. 2008 Mar 05;3(3):e1719 PMID: 18320040
  5. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer.
    Cancer Cell. 2008 Mar;13(3):272-86 PMID: 18328430
  6. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130.
    Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2889-94 PMID: 18287052
  7. Versican mediates mesenchymal-epithelial transition.
    Mol Biol Cell. 2006 Apr;17(4):2009-20 PMID: 16452631
  8. MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression.
    Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20350-5 PMID: 18077375
  9. c-Myc-regulated microRNAs modulate E2F1 expression.
    Nature. 2005 Jun 9;435(7043):839-43 PMID: 15944709
  10. MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.
    PLoS One. 2006 Dec 27;1:e116 PMID: 17205120
  11. The ability of versican to simultaneously cause apoptotic resistance and sensitivity.
    Cancer Res. 2007 May 15;67(10):4742-50 PMID: 17510402
  12. miRiad roles for the miR-17-92 cluster in development and disease.
    Cell. 2008 Apr 18;133(2):217-22 PMID: 18423194
  13. Oncogenic potential of the miR-106-363 cluster and its implication in human T-cell leukemia.
    Cancer Res. 2007 Jun 15;67(12):5699-707 PMID: 17575136
  14. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA.
    Mol Cell Biol. 2006 Nov;26(21):8191-201 PMID: 16940181
  15. A role for fibronectin-leucine-rich transmembrane cell-surface proteins in homotypic cell adhesion.
    EMBO Rep. 2006 Mar;7(3):283-90 PMID: 16440004
  16. The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis.
    Breast Cancer Res. 2007;9(4):R47 PMID: 17662123
  17. microRNAs exhibit high frequency genomic alterations in human cancer.
    Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9136-41 PMID: 16754881
  18. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment.
    Nat Cell Biol. 2008 Aug;10(8):987-93 PMID: 18604195
  19. MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression.
    Mol Cell Biol. 2008 Apr;28(7):2167-74 PMID: 18212054
  20. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes.
    Nat Immunol. 2008 Apr;9(4):405-14 PMID: 18327259
  21. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
    Cell. 2008 Mar 7;132(5):875-86 PMID: 18329372
  22. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin.
    Nature. 2003 Jul 17;424(6946):334-7 PMID: 12867986
  23. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster.
    Nat Genet. 2006 Sep;38(9):1060-5 PMID: 16878133
  24. Mesodermal development in mouse embryos mutant for fibronectin.
    Dev Dyn. 1996 Oct;207(2):145-56 PMID: 8906418
  25. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma.
    Cancer Res. 2004 May 1;64(9):3087-95 PMID: 15126345
  26. Redefining the role of ectoderm in somitogenesis: a player in the formation of the fibronectin matrix of presomitic mesoderm.
    Development. 2007 Sep;134(17):3155-65 PMID: 17670788
  27. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92.
    Oncogene. 2007 Sep 6;26(41):6099-105 PMID: 17384677
  28. An E2F/miR-20a autoregulatory feedback loop.
    J Biol Chem. 2007 Jan 26;282(4):2135-43 PMID: 17135249
  29. The roles of versican V1 and V2 isoforms in cell proliferation and apoptosis.
    Mol Biol Cell. 2005 Mar;16(3):1330-40 PMID: 15635104
  30. A 3'-untranslated region (3'UTR) induces organ adhesion by regulating miR-199a* functions.
    PLoS One. 2009;4(2):e4527 PMID: 19223980
  31. MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation.
    Nat Cell Biol. 2007 Jul;9(7):775-87 PMID: 17589498
  32. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation.
    Cancer Res. 2005 Nov 1;65(21):9628-32 PMID: 16266980
  33. The nuclear RNase III Drosha initiates microRNA processing.
    Nature. 2003 Sep 25;425(6956):415-9 PMID: 14508493
  34. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells.
    Dev Biol. 2007 Oct 15;310(2):442-53 PMID: 17765889
  35. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223.
    Nature. 2008 Feb 28;451(7182):1125-9 PMID: 18278031
  36. Vertebrate microRNA genes.
    Science. 2003 Mar 7;299(5612):1540 PMID: 12624257
  37. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.
    Nat Cell Biol. 2008 May;10(5):593-601 PMID: 18376396
  38. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.
    PLoS One. 2008 Jun 18;3(6):e2420 PMID: 18560585
Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb1917
Published
2009-08-00
Epub
2009-00-26
Pages
1031-8
Language
English
Region
England
NLM ID
100890575
Subset
IM
External Links
PubMed source DOI: 10.1038/ncb1917 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: product@genelibs.com

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