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Small RNAs as Potential Platelet Therapeutics

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 210))

Abstract

MicroRNAs (miRNAs) are 21-23 nucleotide RNAs that regulate more than 60% of mammalian protein coding genes. miRNAs play critical roles in hematopoiesis and megakaryocyte function and development. Platelets, in addition to possessing functional miRNA processing machinery, have miRNA levels that have been correlated with platelet reactivity, and these miRNAs have been shown to target mRNAs that encode proteins that alter platelet function. There are potential uses of platelet miRNA as biomarkers and therapeutic agents. Due to the ability of platelets to release miRNA-containing microparticles at sites of activation, including angiogenic regions, tumors, and atherosclerotic plaques, there is the possibility of engineering platelets to deliver miRNA-based therapies to these sites. Cellpreferential expression of miRNAs could be exploited to restrict transgene expression in hematopoietic stem cell gene therapy to the desired lineage, including megakaryocytes and platelets. Finally, manipulation of gene expression in stored platelets may allow more effective platelet storage. Although much work remains to be done, there is great potential in miRNA-based platelet therapies.

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References

  • Anand S, Majeti BK, Acevedo LM et al (2010) MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med 16:909–914

    Article  PubMed  CAS  Google Scholar 

  • Bandiera S, Hatem E, Lyonnet S et al (2010) microRNAs in diseases: from candidate to modifier genes. Clin Genet 77:306–313

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  • Bonauer A, Carmona G, Iwasaki M et al (2009) MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324:1710–1713

    Article  PubMed  CAS  Google Scholar 

  • Bruchova H, Merkerova M, Prchal JT (2008) Aberrant expression of microRNA in polycythemia vera. Haematologica 93:1009–1016

    Article  PubMed  CAS  Google Scholar 

  • Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10:1957–1966

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Ferracin M, Cimmino A et al (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353:1793–1801

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Ridzon DA, Broomer AJ et al (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179

    Article  PubMed  Google Scholar 

  • Chen X, Ba Y, Ma L et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006

    Article  PubMed  CAS  Google Scholar 

  • Doebele C, Bonauer A, Fischer A et al (2010) Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood 115:4944–4950

    Article  PubMed  CAS  Google Scholar 

  • Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726

    Article  PubMed  CAS  Google Scholar 

  • Edelstein LC, Bray PF (2011) MicroRNAs in platelet production and activation. Blood 117:5289–5296

    Article  PubMed  CAS  Google Scholar 

  • Garzon R, Croce CM (2008) MicroRNAs in normal and malignant hematopoiesis. Curr Opin Hematol 15:352–358

    Article  PubMed  CAS  Google Scholar 

  • Geiss GK, Bumgarner RE, Birditt B et al (2008) Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 26:317–325

    Article  PubMed  CAS  Google Scholar 

  • Gillitzer A, Peluso M, Laugwitz KL et al (2005) Retroviral infection and selection of culture-derived platelets allows study of the effect of transgenes on platelet physiology ex vivo and on thrombus formation in vivo. Arterioscler Thromb Vasc Biol 25:1750–1755

    Article  PubMed  CAS  Google Scholar 

  • Greene TK, Wang C, Hirsch JD et al (2010) In vivo efficacy of platelet-delivered, high specific activity factor VIII variants. Blood 116:6114–6122

    Article  PubMed  CAS  Google Scholar 

  • Griffiths-Jones S, Saini HK, van Dongen S et al (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158

    Article  PubMed  CAS  Google Scholar 

  • Hoffmeister KM, Felbinger TW, Falet H et al (2003) The clearance mechanism of chilled blood platelets. Cell 112:87–97

    Article  PubMed  CAS  Google Scholar 

  • Hong W, Kondkar AA, Nagalla S et al (2011) Transfection of human platelets with short interfering RNA. Clin Transl Sci 4:180–182

    Article  PubMed  CAS  Google Scholar 

  • Hunter MP, Ismail N, Zhang X et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694

    Article  PubMed  Google Scholar 

  • Ji J, Shi J, Budhu A et al (2009) MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 361:1437–1447

    Article  PubMed  CAS  Google Scholar 

  • Kim CW, Lee HM, Lee TH et al (2002) Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res 62:6312–6317

    PubMed  CAS  Google Scholar 

  • Kim HK, Song KS, Chung JH et al (2004) Platelet microparticles induce angiogenesis in vitro. Br J Haematol 124:376–384

    Article  PubMed  Google Scholar 

  • Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139

    Article  PubMed  CAS  Google Scholar 

  • Kondkar AA, Bray MS, Leal SM et al (2010) VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 8:369–378

    Article  PubMed  CAS  Google Scholar 

  • Krutzfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689

    Article  PubMed  Google Scholar 

  • Kurreck J (2003) Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem 270:1628–1644

    Article  PubMed  CAS  Google Scholar 

  • Landry P, Plante I, Ouellet DL et al (2009) Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 16:961–966

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Kim M, Han J et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Getz G, Miska EA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Reinhardt F, Pan E et al (2010) Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28:341–347

    Article  PubMed  CAS  Google Scholar 

  • Molnar A, Melnyk CW, Bassett A et al (2010) Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells. Science 328:872–875

    Article  PubMed  CAS  Google Scholar 

  • Nagalla S, Shaw C, Kong X et al (2011) Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 117:5189–5197

    Article  PubMed  CAS  Google Scholar 

  • Nana-Sinkam SP, Croce CM (2011) MicroRNAs as therapeutic targets in cancer. Transl Res 157:216–225

    Article  PubMed  CAS  Google Scholar 

  • Poliseno L, Salmena L, Zhang J et al (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–1038

    Article  PubMed  CAS  Google Scholar 

  • Qiao C, Yuan Z, Li J et al (2011) Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver. Gene Ther 18:403–410

    Article  PubMed  CAS  Google Scholar 

  • Sethupathy P, Collins FS (2008) MicroRNA target site polymorphisms and human disease. Trends Genet 24:489–497

    Article  PubMed  CAS  Google Scholar 

  • Slupsky JR, Kalbas M, Willuweit A et al (1998) Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40. Thromb Haemost 80:1008–1014

    PubMed  CAS  Google Scholar 

  • Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  PubMed  CAS  Google Scholar 

  • Thon JN, Devine DV (2007) Translation of glycoprotein IIIa in stored blood platelets. Transfusion 47:2260–2270

    Article  PubMed  CAS  Google Scholar 

  • Thum T, Gross C, Fiedler J et al (2008) MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456:980–984

    Article  PubMed  CAS  Google Scholar 

  • Verheul HM, Hoekman K, Luykx-de Bakker S et al (1997) Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 3:2187–2190

    PubMed  CAS  Google Scholar 

  • Wartiovaara U, Salven P, Mikkola H et al (1998) Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation. Thromb Haemost 80:171–175

    PubMed  CAS  Google Scholar 

  • Weber JA, Baxter DH, Zhang S et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56:1733–1741

    Article  PubMed  CAS  Google Scholar 

  • Wienholds E, Kloosterman WP, Miska E et al (2005) MicroRNA expression in zebrafish embryonic development. Science 309:310–311

    Article  PubMed  CAS  Google Scholar 

  • Ye Z, Yu X, Cheng L (2008) Lentiviral gene transduction of mouse and human stem cells. Methods Mol Biol 430:243–253

    Article  PubMed  CAS  Google Scholar 

  • Yuan A, Farber EL, Rapoport AL et al (2009) Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One 4:e4722

    Article  PubMed  Google Scholar 

Download references

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Correspondence to Paul F. Bray M.D. .

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© 2012 Springer-Verlag Berlin Heidelberg

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Edelstein, L.C., Bray, P.F. (2012). Small RNAs as Potential Platelet Therapeutics. In: Gresele, P., Born, G., Patrono, C., Page, C. (eds) Antiplatelet Agents. Handbook of Experimental Pharmacology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29423-5_17

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