Home LiteratureArticle Details
PMID: 22303391 Published · epublish English Journal Article

Unraveling the Mystery of Cancer by Secretory microRNA: Horizontal microRNA Transfer between Living Cells.

Frontiers in genetics ·Vol. 2 ·2011-00-00 ·Pages 97

Kosaka N, Ochiya T

Abstract

microRNAs (miRNAs) have been identified as a fine-tuner in a wide array of biological processes, including development, organogenesis, metabolism, and homeostasis. Deregulation of miRNAs causes diseases, especially cancer. This occurs through a variety of mechanisms, such as genetic alterations, epigenetic regulation, or altered expression of transcription factors, which target miRNAs. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients. Since RNase is abundant in the bloodstream, most of the secretory miRNAs are contained in apoptotic bodies, microvesicles, and exosomes or bound to the RNA-binding proteins. However, the secretory mechanism and biological function, as well as the significance of extracellular miRNAs, remain largely unclear. In this article, we summarize the latest and most significant discoveries in recent peer-reviewed research on secretory miRNA involvement in many aspects of physiological and pathological conditions, with a special focus on cancer. In addition, we discuss a new aspect of cancer research that is revealed by the emergence of "secretory miRNA."

Keywords
cancer cell–cell communication exosome microRNA secretory microRNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kosaka Nobuyoshi
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute Tokyo, Japan.
Ochiya Takahiro
References (43)
43 references, click to expand
  1. Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells.
    Science. 2010 May 14;328(5980):872-5 PMID: 20413459
  2. Small RNAs are on the move.
    Nature. 2010 Sep 23;467(7314):415-9 PMID: 20864994
  3. Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth.
    Hepatology. 2011 Oct;54(4):1237-48 PMID: 21721029
  4. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma.
    Br J Haematol. 2008 May;141(5):672-5 PMID: 18318758
  5. Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1.
    Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2283-8 PMID: 19168628
  6. Export of microRNAs and microRNA-protective protein by mammalian cells.
    Nucleic Acids Res. 2010 Nov;38(20):7248-59 PMID: 20615901
  7. Elevated serum ribonuclease in patients with pancreatic cancer.
    Proc Natl Acad Sci U S A. 1976 Jul;73(7):2308-10 PMID: 1065880
  8. Presence of RNA in the nucleoprotein complex spontaneously released by human lymphocytes and frog auricles in culture.
    Cancer Res. 1978 Oct;38(10):3546-54 PMID: 688240
  9. Targeting microRNAs in cancer: rationale, strategies and challenges.
    Nat Rev Drug Discov. 2010 Oct;9(10):775-89 PMID: 20885409
  10. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis.
    Cancer Sci. 2010 Oct;101(10):2087-92 PMID: 20624164
  11. Hallmarks of cancer: the next generation.
    Cell. 2011 Mar 4;144(5):646-74 PMID: 21376230
  12. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity.
    Nat Cell Biol. 2009 Sep;11(9):1143-9 PMID: 19684575
  13. Small RNA duplexes function as mobile silencing signals between plant cells.
    Science. 2010 May 14;328(5980):912-6 PMID: 20413458
  14. Detection and characterization of placental microRNAs in maternal plasma.
    Clin Chem. 2008 Mar;54(3):482-90 PMID: 18218722
  15. Transport of dsRNA into cells by the transmembrane protein SID-1.
    Science. 2003 Sep 12;301(5639):1545-7 PMID: 12970568
  16. Circulating nucleic acids (CNAs) and cancer--a survey.
    Biochim Biophys Acta. 2007 Jan;1775(1):181-232 PMID: 17137717
  17. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
    Nat Cell Biol. 2011 Apr;13(4):423-33 PMID: 21423178
  18. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.
    Science. 2008 Feb 29;319(5867):1244-7 PMID: 18309083
  19. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma.
    Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8 PMID: 21383194
  20. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA.
    Cell Res. 2012 Jan;22(1):107-26 PMID: 21931358
  21. Secretory mechanisms and intercellular transfer of microRNAs in living cells.
    J Biol Chem. 2010 Jun 4;285(23):17442-52 PMID: 20353945
  22. Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells.
    Virol J. 2010 Oct 15;7:271 PMID: 20950422
  23. RNA interference: a mammalian SID-1 homologue enhances siRNA uptake and gene silencing efficacy in human cells.
    Biochem Biophys Res Commun. 2005 Jun 3;331(2):459-63 PMID: 15850781
  24. Stability of endogenous and added RNA in blood specimens, serum, and plasma.
    Clin Chem. 2002 Oct;48(10):1647-53 PMID: 12324479
  25. RNAs as extracellular signaling molecules.
    J Mol Endocrinol. 2008 Apr;40(4):151-9 PMID: 18372404
  26. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage.
    Circ Cardiovasc Genet. 2011 Aug 1;4(4):446-54 PMID: 21642241
  27. Evidence for transfer of macromolecular RNA between mammalian cells in culture.
    Exp Cell Res. 1971 Apr;65(2):313-24 PMID: 4101797
  28. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
    Nat Cell Biol. 2007 Jun;9(6):654-9 PMID: 17486113
  29. Functional delivery of viral miRNAs via exosomes.
    Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6328-33 PMID: 20304794
  30. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells.
    Exp Cell Res. 2011 May 1;317(8):1192-202 PMID: 21276792
  31. Nuclear Acids In Human Blood Plasma.
    C R Seances Soc Biol Fil. 1948 Feb;142(3-4):241-3 PMID: 18875018
  32. Diagnostic and prognostic value of RNA-proteolipid in sera of patients with malignant disorders following therapy: first clinical evaluation of a novel tumor marker.
    Cancer Res. 1987 Dec 1;47(23):6407-12 PMID: 2445471
  33. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection.
    Sci Signal. 2009 Dec 08;2(100):ra81 PMID: 19996457
  34. Microvesicles: mediators of extracellular communication during cancer progression.
    J Cell Sci. 2010 May 15;123(Pt 10):1603-11 PMID: 20445011
  35. An "external" RNA removable from mammalian cells by mild proteolysis.
    Proc Natl Acad Sci U S A. 1974 Dec;71(12):4960-4 PMID: 4531029
  36. The microRNA pathway and cancer.
    Cancer Sci. 2010 Nov;101(11):2309-15 PMID: 20726859
  37. Uptake of exogenous ribonucleic acid by ascites tumor cells. II. Relations between RNA uptake and the cellular metabolism.
    Exp Cell Res. 1966 Sep;43(2):391-7 PMID: 5919899
  38. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.
    Cancer Res. 2011 Jun 1;71(11):3792-801 PMID: 21478294
  39. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid.
    Nature. 1953 Apr 25;171(4356):737-8 PMID: 13054692
  40. Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells.
    Cancer Res. 2011 Mar 1;71(5):1550-60 PMID: 21343399
  41. Secreted monocytic miR-150 enhances targeted endothelial cell migration.
    Mol Cell. 2010 Jul 9;39(1):133-44 PMID: 20603081
  42. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells.
    Nat Commun. 2011;2:282 PMID: 21505438
  43. Characterization of extracellular circulating microRNA.
    Nucleic Acids Res. 2011 Sep 1;39(16):7223-33 PMID: 21609964
Article Info
Journal
Frontiers in genetics
Abbr.
Front Genet
ISSN
1664-8021
Published
2011-00-00
Epub
2012-00-03
Pages
97
Language
English
Region
Switzerland
NLM ID
101560621
PMCID
PMC3262223
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