RSS-Feed abonnieren
DOI: 10.1055/s-0040-1718730
Methods to Investigate miRNA Function: Focus on Platelet Reactivity
Funding This work was supported by the Private Foundation of the University Hospitals of Geneva (grant RC04–05).Abstract
MicroRNAs (miRNAs) are small noncoding RNAs modulating protein production. They are key players in regulation of cell function and are considered as biomarkers in several diseases. The identification of the proteins they regulate, and their impact on cell physiology, may delineate their role as diagnostic or prognostic markers and identify new therapeutic strategies. During the last 3 decades, development of a large panel of techniques has given rise to multiple models dedicated to the study of miRNAs. Since plasma samples are easily accessible, circulating miRNAs can be studied in clinical trials. To quantify miRNAs in numerous plasma samples, the choice of extraction and purification techniques, as well as normalization procedures, are important for comparisons of miRNA levels in populations and over time. Recent advances in bioinformatics provide tools to identify putative miRNAs targets that can then be validated with dedicated assays. In vitro and in vivo approaches aim to functionally validate candidate miRNAs from correlations and to understand their impact on cellular processes. This review describes the advantages and pitfalls of the available techniques for translational research to study miRNAs with a focus on their role in regulating platelet reactivity.
Authors' Contributions
A.G. had the initial idea and conceptualized this work, A.G., S.D.-G., and P.F. wrote the first draft of the manuscript. J.-L.R., M.N.-A., and R.J.F. critically revised the manuscript. All authors approved the manuscript.
Publikationsverlauf
Eingereicht: 09. Juli 2020
Angenommen: 08. September 2020
Artikel online veröffentlicht:
29. Oktober 2020
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Thon JN, Italiano JE. Platelet formation. Semin Hematol 2010; 47 (03) 220-226
- 2 Bray PF, Mathias RA, Faraday N. et al. Heritability of platelet function in families with premature coronary artery disease. J Thromb Haemost 2007; 5 (08) 1617-1623
- 3 Reny JL, De Moerloose P, Dauzat M, Fontana P. Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2008; 6 (03) 444-450
- 4 Combescure C, Fontana P, Mallouk N. et al. CLOpidogrel and Vascular ISchemic Events Meta-analysis Study Group. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost 2010; 8 (05) 923-933
- 5 Tantry US, Gurbel PA. Antiplatelet drug resistance and variability in response: the role of antiplatelet therapy monitoring. Curr Pharm Des 2013; 19 (21) 3795-3815
- 6 Shuldiner AR, O'Connell JR, Bliden KP. et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009; 302 (08) 849-857
- 7 Edelstein LC, McKenzie SE, Shaw C, Holinstat MA, Kunapuli SP, Bray PF. MicroRNAs in platelet production and activation. J Thromb Haemost 2013; 11 (Suppl. 01) 340-350
- 8 Willeit P, Zampetaki A, Dudek K. et al. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res 2013; 112 (04) 595-600
- 9 Kaudewitz D, Skroblin P, Bender LH. et al. Association of MicroRNAs and YRNAs with platelet function. Circ Res 2016; 118 (03) 420-432
- 10 Shi R, Zhou X, Ji WJ. et al. The emerging role of miR-223 in platelet reactivity: implications in antiplatelet therapy. BioMed Res Int 2015; 2015: 981841
- 11 Zufferey A, Ibberson M, Reny JL. et al. New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach. Hum Genet 2016; 135 (04) 403-414
- 12 Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 2017; 6 (02) E16
- 13 Leblanc R, Peyruchaud O. Metastasis: new functional implications of platelets and megakaryocytes. Blood 2016; 128 (01) 24-31
- 14 Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19 (01) 92-105
- 15 Semple JW, Italiano Jr JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011; 11 (04) 264-274
- 16 Leblanc R, Houssin A, Peyruchaud O. Platelets, autotaxin and lysophosphatidic acid signalling: win-win factors for cancer metastasis. Br J Pharmacol 2018; 175 (15) 3100-3110
- 17 Alles J, Fehlmann T, Fischer U. et al. An estimate of the total number of true human miRNAs. Nucleic Acids Res 2019; 47 (07) 3353-3364
- 18 Plé H, Landry P, Benham A, Coarfa C, Gunaratne PH, Provost P. The repertoire and features of human platelet microRNAs. PLoS One 2012; 7 (12) e50746
- 19 Landry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 2009; 16 (09) 961-966
- 20 Arroyo JD, Chevillet JR, Kroh EM. et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 2011; 108 (12) 5003-5008
- 21 O'Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol 2020
- 22 Provost P. The clinical significance of platelet microparticle-associated microRNAs. Clin Chem Lab Med 2017; 55 (05) 657-666
- 23 Diehl P, Fricke A, Sander L. et al. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res 2012; 93 (04) 633-644
- 24 Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009; 11 (03) 228-234
- 25 Yang JS, Lai EC. Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell 2011; 43 (06) 892-903
- 26 Desvignes T, Batzel P, Berezikov E. et al. miRNA nomenclature: a view incorporating genetic origins, biosynthetic pathways, and sequence variants. Trends Genet 2015; 31 (11) 613-626
- 27 Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007; 27 (01) 91-105
- 28 Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136 (02) 215-233
- 29 Xia L, Zeng Z, Tang WH. The role of platelet microparticle associated microRNAs in cellular crosstalk. Front Cardiovasc Med 2018; 5: 29
- 30 Camaioni C, Gustapane M, Cialdella P, Della Bona R, Biasucci LM. Microparticles and microRNAs: new players in the complex field of coagulation. Intern Emerg Med 2013; 8 (04) 291-296
- 31 Anene C, Graham AM, Boyne J, Roberts W. Platelet microparticle delivered microRNA-Let-7a promotes the angiogenic switch. Biochim Biophys Acta Mol Basis Dis 2018; 1864 (08) 2633-2643
- 32 Sunderland N, Skroblin P, Barwari T. et al. MicroRNA biomarkers and platelet reactivity: the clot thickens. Circ Res 2017; 120 (02) 418-435
- 33 Kondkar AA, Bray MS, Leal SM. et al. VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 2010; 8 (02) 369-378
- 34 Shi R, Ge L, Zhou X. et al. Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity. Thromb Res 2013; 131 (06) 508-513
- 35 Fontana P, Roffi M, Reny JL. Platelet function test use for patients with coronary artery disease in the early 2020s. J Clin Med 2020; 9 (01) E194
- 36 Wang K, Yuan Y, Cho JH, McClarty S, Baxter D, Galas DJ. Comparing the MicroRNA spectrum between serum and plasma. PLoS One 2012; 7 (07) e41561
- 37 Kaudewitz D, Lee R, Willeit P. et al. Impact of intravenous heparin on quantification of circulating microRNAs in patients with coronary artery disease. Thromb Haemost 2013; 110 (03) 609-615
- 38 Fejes Z, Póliska S, Czimmerer Z. et al. Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb Haemost 2017; 117 (03) 529-542
- 39 Cazenave JP, Ohlmann P, Cassel D, Eckly A, Hechler B, Gachet C. Preparation of washed platelet suspensions from human and rodent blood. Methods Mol Biol 2004; 272: 13-28
- 40 Tran JQD, Pedersen OH, Larsen ML. et al. Platelet microRNA expression and association with platelet maturity and function in patients with essential thrombocythemia. Platelets 2020; 31 (03) 365-372
- 41 Binderup HG, Madsen JS, Heegaard NHH, Houlind K, Andersen RF, Brasen CL. Quantification of microRNA levels in plasma - impact of preanalytical and analytical conditions. PLoS One 2018; 13 (07) e0201069
- 42 Cheng HH, Yi HS, Kim Y. et al. Plasma processing conditions substantially influence circulating microRNA biomarker levels. PLoS One 2013; 8 (06) e64795
- 43 Tiberio P, Callari M, Angeloni V, Daidone MG, Appierto V. Challenges in using circulating miRNAs as cancer biomarkers. BioMed Res Int 2015; 2015: 731479
- 44 Jansen F, Schäfer L, Wang H. et al. Kinetics of circulating MicroRNAs in response to cardiac stress in patients with coronary artery disease. J Am Heart Assoc 2017; 6 (08) e005270
- 45 Zampetaki A, Willeit P, Tilling L. et al. Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 2012; 60 (04) 290-299
- 46 Blondal T, Jensby Nielsen S, Baker A. et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods 2013; 59 (01) S1-S6
- 47 Simon LM, Edelstein LC, Nagalla S. et al. Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics. Blood 2014; 123 (16) e37-e45
- 48 Coenen-Stass AML, Magen I, Brooks T. et al. Evaluation of methodologies for microRNA biomarker detection by next generation sequencing. RNA Biol 2018; 15 (08) 1133-1145
- 49 Pordzik J, Jakubik D, Jarosz-Popek J. et al. Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review. Cardiovasc Diabetol 2019; 18 (01) 113
- 50 Jakob P, Kacprowski T, Briand-Schumacher S. et al. Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction. Eur Heart J 2017; 38 (07) 511-515
- 51 Benz F, Roderburg C, Vargas Cardenas D. et al. U6 is unsuitable for normalization of serum miRNA levels in patients with sepsis or liver fibrosis. Exp Mol Med 2013; 45: e42
- 52 McDonald JS, Milosevic D, Reddi HV, Grebe SK, Algeciras-Schimnich A. Analysis of circulating microRNA: preanalytical and analytical challenges. Clin Chem 2011; 57 (06) 833-840
- 53 Tanaka M, Oikawa K, Takanashi M. et al. Down-regulation of miR-92 in human plasma is a novel marker for acute leukemia patients. PLoS One 2009; 4 (05) e5532
- 54 Zalewski K, Misiek M, Kowalik A. et al. Normalizers for microRNA quantification in plasma of patients with vulvar intraepithelial neoplasia lesions and vulvar carcinoma. Tumour Biol 2017; 39 (11) 1010428317717140
- 55 Mompeón A, Ortega-Paz L, Vidal-Gómez X. et al. Disparate miRNA expression in serum and plasma of patients with acute myocardial infarction: a systematic and paired comparative analysis. Sci Rep 2020; 10 (01) 5373
- 56 Li Y, Xiang GM, Liu LL. et al. Assessment of endogenous reference gene suitability for serum exosomal microRNA expression analysis in liver carcinoma resection studies. Mol Med Rep 2015; 12 (03) 4683-4691
- 57 Kok MG, Halliani A, Moerland PD, Meijers JC, Creemers EE, Pinto-Sietsma SJ. Normalization panels for the reliable quantification of circulating microRNAs by RT-qPCR. FASEB J 2015; 29 (09) 3853-3862
- 58 Garcia A, Dunoyer-Geindre S, Zapilko V, Nolli S, Reny JL, Fontana P. Functional validation of microRNA-126-3p as a platelet reactivity regulator using human haematopoietic stem cells. Thromb Haemost 2019; 119 (02) 254-263
- 59 Chou CH, Lin FM, Chou MT. et al. A computational approach for identifying microRNA-target interactions using high-throughput CLIP and PAR-CLIP sequencing. BMC Genomics 2013; 14 (Suppl. 01) S2
- 60 Hafner M, Landthaler M, Burger L. et al. PAR-CliP–a method to identify transcriptome-wide the binding sites of RNA binding proteins. J Vis Exp 2010; (41) 2034
- 61 Helwak A, Kudla G, Dudnakova T, Tollervey D. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 2013; 153 (03) 654-665
- 62 Steinkraus BR, Toegel M, Fulga TA. Tiny giants of gene regulation: experimental strategies for microRNA functional studies. Wiley Interdiscip Rev Dev Biol 2016; 5 (03) 311-362
- 63 Hafner M, Landthaler M, Burger L. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 2010; 141 (01) 129-141
- 64 Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 2010; 11 (08) R90
- 65 Quillet A, Saad C, Ferry G. et al. Improving bioinformatics prediction of microRNA targets by ranks aggregation. Front Genet 2020; 10: 1330
- 66 Chu YW, Chang KP, Chen CW, Liang YT, Soh ZT, Hsieh LC. miRgo: integrating various off-the-shelf tools for identification of microRNA-target interactions by heterogeneous features and a novel evaluation indicator. Sci Rep 2020; 10 (01) 1466
- 67 Moore AC, Winkjer JS, Tseng TT. Bioinformatics resources for MicroRNA discovery. Biomark Insights 2016; 10 (Suppl. 04) 53-58
- 68 Huntley RP, Sitnikov D, Orlic-Milacic M. et al. Guidelines for the functional annotation of microRNAs using the Gene Ontology. RNA 2016; 22 (05) 667-676
- 69 Deng L, Wang J, Zhang J. Predicting gene ontology function of human MicroRNAs by integrating multiple networks. Front Genet 2019; 10: 3
- 70 Cloonan N. Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery. BioEssays 2015; 37 (04) 379-388
- 71 Tan SM, Lieberman J. Capture and identification of miRNA targets by biotin pulldown and RNA-seq. Methods Mol Biol 2016; 1358: 211-228
- 72 Jin Y, Chen Z, Liu X, Zhou X. Evaluating the microRNA targeting sites by luciferase reporter gene assay. Methods Mol Biol 2013; 936: 117-127
- 73 Bianchi E, Bulgarelli J, Ruberti S. et al. MYB controls erythroid versus megakaryocyte lineage fate decision through the miR-486-3p-mediated downregulation of MAF. Cell Death Differ 2015; 22 (12) 1906-1921
- 74 Hong W, Kondkar AA, Nagalla S. et al. Transfection of human platelets with short interfering RNA. Clin Transl Sci 2011; 4 (03) 180-182
- 75 Edelstein LC, Simon LM, Montoya RT. et al. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nat Med 2013; 19 (12) 1609-1616
- 76 Dhenge A, Kuhikar R, Kale V, Limaye L. Regulation of differentiation of MEG01 to megakaryocytes and platelet-like particles by valproic acid through Notch3 mediated actin polymerization. Platelets 2019; 30 (06) 780-795
- 77 Barwari T, Eminaga S, Mayr U. et al. Inhibition of profibrotic microRNA-21 affects platelets and their releasate. JCI Insight 2018; 3 (21) 123335
- 78 Woolthuis CM, Park CY. Hematopoietic stem/progenitor cell commitment to the megakaryocyte lineage. Blood 2016; 127 (10) 1242-1248
- 79 Sim X, Poncz M, Gadue P, French DL. Understanding platelet generation from megakaryocytes: implications for in vitro-derived platelets. Blood 2016; 127 (10) 1227-1233
- 80 Romania P, Lulli V, Pelosi E, Biffoni M, Peschle C, Marziali G. MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets-1 and Meis1 transcription factors. Br J Haematol 2008; 143 (04) 570-580
- 81 Choi ES, Nichol JL, Hokom MM, Hornkohl AC, Hunt P. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 1995; 85 (02) 402-413
- 82 Sangkuhl K, Shuldiner AR, Klein TE, Altman RB. Platelet aggregation pathway. Pharmacogenet Genomics 2011; 21 (08) 516-521
- 83 Kamat V, Muthard RW, Li R, Diamond SL. Microfluidic assessment of functional culture-derived platelets in human thrombi under flow. Exp Hematol 2015; 43 (10) 891.e4-900.e4
- 84 Auber M, Fröhlich D, Drechsel O, Karaulanov E, Krämer-Albers EM. Serum-free media supplements carry miRNAs that co-purify with extracellular vesicles. J Extracell Vesicles 2019; 8 (01) 1656042
- 85 Basak I, Bhatlekar S, Manne BK. et al. miR-15a-5p regulates expression of multiple proteins in the megakaryocyte GPVI signaling pathway. J Thromb Haemost 2019; 17 (03) 511-524
- 86 Wang T, Larcher LM, Ma L, Veedu RN. Systematic screening of commonly used commercial transfection reagents towards efficient transfection of single-stranded oligonucleotides. Molecules 2018; 23 (10) E2564
- 87 Spinello I, Quaranta MT, Pasquini L. et al. PLZF-mediated control on c-kit expression in CD34(+) cells and early erythropoiesis. Oncogene 2009; 28 (23) 2276-2288
- 88 Diener Y, Bosio A, Bissels U. Delivery of RNA-based molecules to human hematopoietic stem and progenitor cells for modulation of gene expression. Exp Hematol 2016; 44 (11) 991-1001
- 89 Zhou Y, Abraham S, Andre P. et al. Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice. Blood 2015; 126 (26) 2871-2881
- 90 Maurisse R, De Semir D, Emamekhoo H. et al. Comparative transfection of DNA into primary and transformed mammalian cells from different lineages. BMC Biotechnol 2010; 10: 9
- 91 Sharifi Tabar M, Hesaraki M, Esfandiari F, Sahraneshin Samani F, Vakilian H, Baharvand H. Evaluating electroporation and lipofectamine approaches for transient and stable transgene expressions in human fibroblasts and embryonic stem cells. Cell J 2015; 17 (03) 438-450
- 92 Jin HY, Gonzalez-Martin A, Miletic AV. et al. Transfection of microRNA mimics should be used with caution. Front Genet 2015; 6: 340
- 93 Yuan JY, Wang F, Yu J, Yang GH, Liu XL, Zhang JW. MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells. J Cell Mol Med 2009; 13 (11–12): 4551-4559
- 94 Kurreck J. Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem 2003; 270 (08) 1628-1644
- 95 Soifer HS, Koch T, Lai J. et al. Silencing of gene expression by gymnotic delivery of antisense oligonucleotides. Methods Mol Biol 2012; 815: 333-346
- 96 Flierl U, Nero TL, Lim B. et al. Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators. J Exp Med 2015; 212 (02) 129-137
- 97 Cao F, Xie X, Gollan T. et al. Comparison of gene-transfer efficiency in human embryonic stem cells. Mol Imaging Biol 2010; 12 (01) 15-24
- 98 Vian L, Di Carlo M, Pelosi E. et al. Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors. Cell Death Differ 2014; 21 (02) 290-301
- 99 Nazari B, Soleimani M, Ebrahimi-Barough S. et al. Overexpression of miR-219 promotes differentiation of human induced pluripotent stem cells into pre-oligodendrocyte. J Chem Neuroanat 2018; 91: 8-16
- 100 van Til NP, Wagemaker G. Lentiviral gene transduction of mouse and human hematopoietic stem cells. Methods Mol Biol 2014; 1185: 311-319
- 101 Sebrow J, Goff SP, Griffin DO. Successfully transfected primary peripherally mobilized human CD34+ hematopoietic stem and progenitor cells (HSPCs) demonstrate increased susceptibility to retroviral infection. Virol J 2020; 17 (01) 22
- 102 Lataniotis L, Albrecht A, Kok FO. et al. CRISPR/Cas9 editing reveals novel mechanisms of clustered microRNA regulation and function. Sci Rep 2017; 7 (01) 8585
- 103 Kim YK, Wee G, Park J. et al. TALEN-based knockout library for human microRNAs. Nat Struct Mol Biol 2013; 20 (12) 1458-1464
- 104 Mir P, Ritter M, Welte K, Skokowa J, Klimiankou M. Gene knockout in hematopoietic stem and progenitor cells followed by granulocytic differentiation. Methods Mol Biol 2020; 2115: 455-469
- 105 Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75 (05) 843-854
- 106 Carthew RW, Agbu P, Giri R. MicroRNA function in Drosophila melanogaster. Semin Cell Dev Biol 2017; 65: 29-37
- 107 Schier AF, Giraldez AJ. MicroRNA function and mechanism: insights from zebra fish. Cold Spring Harb Symp Quant Biol 2006; 71: 195-203
- 108 Lewis MA, Steel KP. MicroRNAs in mouse development and disease. Semin Cell Dev Biol 2010; 21 (07) 774-780
- 109 Pal AS, Kasinski AL. Animal models to study MicroRNA function. Adv Cancer Res 2017; 135: 53-118
- 110 Lang MR, Gihr G, Gawaz MP, Müller II. Hemostasis in Danio rerio: is the zebrafish a useful model for platelet research?. J Thromb Haemost 2010; 8 (06) 1159-1169
- 111 Gregory M, Hanumanthaiah R, Jagadeeswaran P. Genetic analysis of hemostasis and thrombosis using vascular occlusion. Blood Cells Mol Dis 2002; 29 (03) 286-295
- 112 Lin HF, Traver D, Zhu H. et al. Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood 2005; 106 (12) 3803-3810
- 113 Roberto VP, Tiago DM, Gautvik K, Cancela ML. Evidence for the conservation of miR-223 in zebrafish (Danio rerio): Implications for function. Gene 2015; 566 (01) 54-62
- 114 Zapilko V, Fish RJ, Garcia A. et al. MicroRNA-126 is a regulator of platelet-supported thrombin generation. Platelets 2020; 31 (06) 746-755
- 115 Dong M, Fu YF, Du TT. et al. Heritable and lineage-specific gene knockdown in zebrafish embryo. PLoS One 2009; 4 (07) e6125
- 116 Thermes V, Grabher C, Ristoratore F. et al. I-SceI meganuclease mediates highly efficient transgenesis in fish. Mech Dev 2002; 118 (1–2): 91-98
- 117 Abe G, Suster ML, Kawakami K. Tol2-mediated transgenesis, gene trapping, enhancer trapping, and the Gal4-UAS system. Methods Cell Biol 2011; 104: 23-49
- 118 Suster ML, Abe G, Schouw A, Kawakami K. Transposon-mediated BAC transgenesis in zebrafish. Nat Protoc 2011; 6 (12) 1998-2021
- 119 Haffter P, Granato M, Brand M. et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 1996; 123: 1-36
- 120 Housden BE, Muhar M, Gemberling M. et al. Loss-of-function genetic tools for animal models: cross-species and cross-platform differences. Nat Rev Genet 2017; 18 (01) 24-40
- 121 Bassett AR, Azzam G, Wheatley L. et al. Understanding functional miRNA-target interactions in vivo by site-specific genome engineering. Nat Commun 2014; 5: 4640
- 122 Hwang WY, Fu Y, Reyon D. et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 2013; 31 (03) 227-229
- 123 Wienholds E, van Eeden F, Kosters M, Mudde J, Plasterk RH, Cuppen E. Efficient target-selected mutagenesis in zebrafish. Genome Res 2003; 13 (12) 2700-2707
- 124 Fish RJ, Di Sanza C, Neerman-Arbez M. Targeted mutation of zebrafish fga models human congenital afibrinogenemia. Blood 2014; 123 (14) 2278-2281
- 125 Gut P, Reischauer S, Stainier DYR, Arnaout R. Little fish, big data: zebrafish as a model for cardiovascular and metabolic disease. Physiol Rev 2017; 97 (03) 889-938
- 126 Howe K, Clark MD, Torroja CF. et al. The zebrafish reference genome sequence and its relationship to the human genome. Nature 2013; 496 (7446): 498-503
- 127 Yin VP, Lepilina A, Smith A, Poss KD. Regulation of zebrafish heart regeneration by miR-133. Dev Biol 2012; 365 (02) 319-327
- 128 Giacomotto J, Rinkwitz S, Becker TS. Effective heritable gene knockdown in zebrafish using synthetic microRNAs. Nat Commun 2015; 6: 7378
- 129 Stainier DYR, Raz E, Lawson ND. et al. Guidelines for morpholino use in zebrafish. PLoS Genet 2017; 13 (10) e1007000
- 130 Zou J, Li WQ, Li Q. et al. Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish. Circ Res 2011; 108 (02) 201-209
- 131 Shestopalov IA, Chen JK. Oligonucleotide-based tools for studying zebrafish development. Zebrafish 2010; 7 (01) 31-40
- 132 Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA 2010; 16 (11) 2043-2050
- 133 Bak RO, Hollensen AK, Mikkelsen JG. Managing microRNAs with vector-encoded decoy-type inhibitors. Mol Ther 2013; 21 (08) 1478-1485
- 134 Lee KT, Nam JW. Post-transcriptional and translational regulation of mRNA-like long non-coding RNAs by microRNAs in early developmental stages of zebrafish embryos. BMB Rep 2017; 50 (04) 226-231
- 135 Bernardo BC, Gregorevic P, Ritchie RH, McMullen JR. Generation of MicroRNA-34 sponges and tough decoys for the heart: developments and challenges. Front Pharmacol 2018; 9: 1090
- 136 Gays D, Santoro MM. The admiR-able advances in cardiovascular biology through the zebrafish model system. Cell Mol Life Sci 2013; 70 (14) 2489-2503
- 137 Mohammed BM, Monroe DM, Gailani D. Mouse models of hemostasis. Platelets 2020; 31 (04) 417-422
- 138 Rivera J, Lozano ML, Navarro-Núñez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica 2009; 94 (05) 700-711
- 139 Roux J, Gonzàlez-Porta M, Robinson-Rechavi M. Comparative analysis of human and mouse expression data illuminates tissue-specific evolutionary patterns of miRNAs. Nucleic Acids Res 2012; 40 (13) 5890-5900
- 140 Park CY, Choi YS, McManus MT. Analysis of microRNA knockouts in mice. Hum Mol Genet 2010; 19 (R2): R169-R175
- 141 Prosser HM, Koike-Yusa H, Cooper JD, Law FC, Bradley A. A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nat Biotechnol 2011; 29 (09) 840-845
- 142 Leierseder S, Petzold T, Zhang L, Loyer X, Massberg S, Engelhardt S. MiR-223 is dispensable for platelet production and function in mice. Thromb Haemost 2013; 110 (06) 1207-1214
- 143 Kleinhammer A, Deussing J, Wurst W, Kühn R. Conditional RNAi in mice. Methods 2011; 53 (02) 142-150
- 144 Park CY, Jeker LT, Carver-Moore K. et al. A resource for the conditional ablation of microRNAs in the mouse. Cell Rep 2012; 1 (04) 385-391
- 145 Tiedt R, Schomber T, Hao-Shen H, Skoda RC. Pf4-Cre transgenic mice allow the generation of lineage-restricted gene knockouts for studying megakaryocyte and platelet function in vivo. Blood 2007; 109 (04) 1503-1506
- 146 Rowley JW, Chappaz S, Corduan A. et al. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood 2016; 127 (14) 1743-1751
- 147 Boilard E, Belleannée C. (Dicer)phering roles of microRNA in platelets. Blood 2016; 127 (14) 1733-1734
- 148 Nagy Z, Vögtle T, Geer MJ. et al. The Gp1ba-Cre transgenic mouse: a new model to delineate platelet and leukocyte functions. Blood 2019; 133 (04) 331-343
- 149 Takada S, Sato T, Ito Y. et al. Targeted gene deletion of miRNAs in mice by TALEN system. PLoS One 2013; 8 (10) e76004
- 150 Chang H, Yi B, Ma R, Zhang X, Zhao H, Xi Y. CRISPR/cas9, a novel genomic tool to knock down microRNA in vitro and in vivo. Sci Rep 2016; 6: 22312
- 151 Yasue A, Mitsui SN, Watanabe T. et al. Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems. Sci Rep 2014; 4: 5705
- 152 Zeng LL, He XS, Liu JR, Zheng CB, Wang YT, Yang GY. Lentivirus-mediated overexpression of MicroRNA-210 improves long-term outcomes after focal cerebral ischemia in mice. CNS Neurosci Ther 2016; 22 (12) 961-969
- 153 Tsumaru S, Masumoto H, Minakata K. et al. Therapeutic angiogenesis by local sustained release of microRNA-126 using poly lactic-co-glycolic acid nanoparticles in murine hindlimb ischemia. J Vasc Surg 2018; 68 (04) 1209-1215
- 154 Witkowski M, Weithauser A, Tabaraie T. et al. Micro-RNA-126 reduces the blood thrombogenicity in diabetes mellitus via targeting of tissue factor. Arterioscler Thromb Vasc Biol 2016; 36 (06) 1263-1271
- 155 Peng L, Liu J, Qin L. et al. Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS. Thromb Res 2017; 157: 97-102
- 156 Ding T, Zeng X, Cheng B. et al. Platelets in acute coronary syndrome patients with high platelet reactivity after dual antiplatelet therapy exhibit upregulation of miR-204-5p. Ann Clin Lab Sci 2019; 49 (05) 619-631
- 157 Tang QJ, Lei HP, Wu H. et al. Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy. Acta Pharmacol Sin 2019; 40 (02) 208-215
- 158 Liu J, Qin L, Wang Z. et al. Platelet-derived miRNAs as determinants of the antiplatelet response in clopidogrel-treated patients with ACS. Thromb Res 2020; 186: 71-74