Deep sequencing of RNA from three different extracellular vesicle (EV) subtypes released from the human LIM1863 colon cancer cell line uncovers distinct mirna-enrichment signatures

PLoS ONE

Volumn 9, Issue 10, 2014, Pages

  Ji, Hong ^a   Chen, Maoshan ^a   Greening, David W ^a   He, Weifeng ^b   Rai, Alin ^a   Zhang, Wenwei ^c   Simpson, Richard J ^a  

^a LA TROBE UNIVERSITY   (Australia)

^b THIRD MILITARY MEDICAL UNIVERSITY   (China)

^c BGI SHENZHEN   (China)

Author keywords

[No Author keywords available]

Indexed keywords

LET 7A 3P; LET 7F 1 3P; MICRORNA; MICRORNA 19A 3P; MICRORNA 19B 3P; MICRORNA 200C 3P; MICRORNA 221 3P; MICRORNA 320A; MICRORNA 320B; MICRORNA 320C; MICRORNA 320D; MICRORNA 3616 3P; MICRORNA 362 3P; MICRORNA 378A; MICRORNA 378C; MICRORNA 378D; MICRORNA 4454; MICRORNA 451A; MICRORNA 574 5P; MICRORNA 577; MICRORNA 625 3P; MICRORNA 6842 3P; MICRORNA 7641; MICRORNA 8; MICRORNA 98 5P; UNCLASSIFIED DRUG; GENETIC MARKER; PRIMER DNA; SMALL INTERFERING RNA;

ANTIBODY AFFINITY; ARTICLE; CANCER CELL LINE; CELL INCLUSION; COLON CARCINOMA; CONTROLLED STUDY; EXOSOME; EXTRACELLULAR VESICLE; GENE ONTOLOGY; HUMAN; HUMAN CELL; MOLECULAR LIBRARY; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA SEQUENCE; SHED MICROVESICLE; VALIDATION STUDY; BIOLOGY; CELL COMMUNICATION; COLORECTAL TUMOR; COMPARATIVE STUDY; GENE EXPRESSION REGULATION; GENETIC MARKER; GENETICS; HIGH THROUGHPUT SEQUENCING; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; REAL TIME POLYMERASE CHAIN REACTION; SECRETION (PROCESS); SEQUENCE ANALYSIS; TRANSMISSION ELECTRON MICROSCOPY; TRANSPORT VESICLE; TUMOR CELL LINE; ULTRASTRUCTURE; WESTERN BLOTTING;

BASE SEQUENCE; BLOTTING, WESTERN; CELL COMMUNICATION; CELL LINE, TUMOR; COLORECTAL NEOPLASMS; COMPUTATIONAL BIOLOGY; DNA PRIMERS; EXOSOMES; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE ONTOLOGY; GENETIC MARKERS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MICRORNAS; MICROSCOPY, ELECTRON, TRANSMISSION; MOLECULAR SEQUENCE DATA; REAL-TIME POLYMERASE CHAIN REACTION; RNA, SMALL INTERFERING; SEQUENCE ANALYSIS, RNA; TRANSPORT VESICLES;

EID: 84908131505     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0110314     Document Type: Article

References (101)

1. Simpson RJ, Lim JW, Moritz RL, Mathivanan S (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6: 267-283.
2. Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: Extracellular organelles important in intercellular communication. J Proteomics 73: 1907-1920.
3. Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, et al. (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56: 293-304.
4. Tauro BJ, Greening DW, Mathias RA, Mathivanan S, Ji H, et al. (2013) Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics 12: 587-598.
5. Tauro BJ, Mathias RA, Greening DW, Gopal SK, Ji H, et al. (2013) Oncogenic H-ras reprograms Madin-Darby canine kidney (MDCK) cell-derived exosomal proteins following epithelial-mesenchymal transition. Mol Cell Proteomics 12: 2148-2159.
6. Ji H, Greening DW, Barnes TW, Lim JW, Tauro BJ, et al. (2013) Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components. Proteomics 13: 1672-1686.
7. Record M, Carayon K, Poirot M, Silvente-Poirot S (2014) Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochimica et biophysica acta 1841: 108-120.
8. Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, et al. (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Comm 2: 282.
9. Mathivanan S, Fahner CJ, Reid GE, Simpson RJ (2012) ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic acids research 40: D1241-1244.
10. Kim DK, Kang B, Kim OY, Choi DS, Lee J, et al. (2013) EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. Journal of extracellular vesicles 2: 20384.
11. Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19: 43-51.
12. Rak J, Guha A (2012) Extracellular vesicles-vehicles that spread cancer genes. Bioessays 34: 489-497.
13. El Andaloussi S, Lakhal S, Mager I, Wood MJ (2013) Exosomes for targeted siRNA delivery across biological barriers. Advanced drug delivery reviews 65: 391-397.
14. Grange C, Tapparo M, Collino F, Vitillo L, Damasco C, et al. (2011) Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res 71: 5346-5356.
15. Hood JL, San RS, Wickline SA (2011) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 71: 3792-3801.
16. Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, et al. (2012) Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration. Cell 151: 1542-1556.
17. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, et al. (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Med 18: 883-891.
18. Mbeunkui F, Johann DJ, Jr. (2009) Cancer and the tumor microenvironment: a review of an essential relationship. Cancer chemotherapy and pharmacology 63: 571-582.
19. Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nature reviews Cancer 9: 285-293.
20. Lujambio A, Lowe SW (2012) The microcosmos of cancer. Nature 482: 347-355.
21. Mittelbrunn M, Sanchez-Madrid F (2012) Intercellular communication: diverse structures for exchange of genetic information. Nature reviews Molecular cell biology 13: 328-335.
22. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, et al. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9: 654-659.
23. Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, et al. (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nature Cell Biol 10: 1470-1476.
24. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, et al. (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14: 249-256.
25. Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, et al. (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119: 756-766.
26. Roccaro AM, Sacco A, Maiso P, Azab AK, Tai YT, et al. (2013) BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. The Journal of clinical investigation 123: 1542-1555.
27. Zhang Y, Liu D, Chen X, Li J, Li L, et al. (2010) Secreted monocytic miR-150 enhances targeted endothelial cell migration. Molecular cell 39: 133-144.
28. Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, et al. (2013) Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell 24: 542-556.
29. Schetter AJ, Okayama H, Harris CC (2012) The role of microRNAs in colorectal cancer. Cancer journal 18: 244-252.
30. Dong Y, Wu WK, Wu CW, Sung JJ, Yu J, et al. (2011) MicroRNA dysregulation in colorectal cancer: a clinical perspective. British journal of cancer 104: 893-898.
31. Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, Perez-Hernandez D, Vazquez J, et al. (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nature communications 4: 2980.
32. Whitehead RH, Jones JK, Gabriel A, Lukies RE (1987) A new colon carcinoma cell line (LIM1863) that grows as organoids with spontaneous differentiation into crypt-like structures in vitro. Cancer research 47: 2683-2689.
33. Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, et al. (2010) Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics 9: 197-208.
34. Audic S, Claverie JM (1997) The significance of digital gene expression profiles. Genome research 7: 986-995.
35. Li R, Yu C, Li Y, Lam TW, Yiu SM, et al. (2009) SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25: 1966-1967.
36. Ye J, Fang L, Zheng H, Zhang Y, Chen J, et al. (2006) WEGO: a web tool for plotting GO annotations. Nucleic acids research 34: W293-297.
37. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B-Stat Methodol 57: 289-300.
38. Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH (2009) Exosomal microRNA: a diagnostic marker for lung cancer. Clinical lung cancer 10: 42-46.
39. Chen TS, Lai RC, Lee MM, Choo AB, Lee CN, et al. (2010) Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic acids research 38: 215-224.
40. Bellingham SA, Coleman BM, Hill AF (2012) Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic acids research 40: 10937-10949.
41. Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, et al. (2006) Prognostic Values of microRNAs in Colorectal Cancer. Biomarker insights 2: 113-121.
42. Wang Q, Huang Z, Ni S, Xiao X, Xu Q, et al. (2012) Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer. PLoS ONE 7: e44398.
43. Corte H, Manceau G, Blons H, Laurent-Puig P (2012) MicroRNA and colorectal cancer. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 44: 195-200.
44. Huang Z, Huang D, Ni S, Peng Z, Sheng W, et al. (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127: 118-126.
45. Xi Y, Shalgi R, Fodstad O, Pilpel Y, Ju J (2006) Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clin Cancer Res 12: 2014-2024.
46. Geng L, Chaudhuri A, Talmon G, Wisecarver JL, Are C, et al. (2013) MicroRNA-192 suppresses liver metastasis of colon cancer. Oncogene: in press.
47. Kato M, Dang V, Wang M, Park JT, Deshpande S, et al. (2013) TGF-beta induces acetylation of chromatin and of Ets-1 to alleviate repression of miR-192 in diabetic nephropathy. Science signaling 6: ra43.
48. Senanayake U, Das S, Vesely P, Alzoughbi W, Frohlich LF, et al. (2012) miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms. Carcinogenesis 33: 1014-1021.
49. Tsai KW, Kao HW, Chen HC, Chen SJ, Lin WC (2009) Epigenetic control of the expression of a primate-specific microRNA cluster in human cancer cells. Epigenetics: official journal of the DNA Methylation Society 4: 587-592.
50. Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, et al. (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13: 272-286.
51. Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, et al. (2008) Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132: 860-874.
52. Mestdagh P, Bostrom AK, Impens F, Fredlund E, Van Peer G, et al. (2010) The miR-17-92 microRNA cluster regulates multiple components of the TGF-beta pathway in neuroblastoma. Molecular cell 40: 762-773.
53. Nair R, Santos L, Awasthi S, von Erlach T, Chow LW, et al. (2014) Extracellular vesicles derived from preosteoblasts influence embryonic stem cell differentiation. Stem cells and development 23(14): 1625-35.
54. Sun JY, Huang Y, Li JP, Zhang X, Wang L, et al. (2012) MicroRNA-320a suppresses human colon cancer cell proliferation by directly targeting beta-catenin. Biochemical and biophysical research communications 420: 787-792.
55. Zhang Y, He X, Liu Y, Ye Y, Zhang H, et al. (2012) microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer. Oncology reports 27: 685-694.
56. le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, et al. (2007) Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. The EMBO journal 26: 3699-3708.
57. Galardi S, Mercatelli N, Giorda E, Massalini S, Frajese GV, et al. (2007) miR-221 and miR-222 expression affects the proliferation potential of human prostate carcinoma cell lines by targeting p27Kip1. The Journal of biological chemistry 282: 23716-23724.
58. Ng EK, Chong WW, Jin H, Lam EK, Shin VY, et al. (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58: 1375-1381.
59. Hur K, Toiyama Y, Takahashi M, Balaguer F, Nagasaka T, et al. (2013) MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 62: 1315-1326.
60. Hu M, Xia M, Chen X, Lin Z, Xu Y, et al. (2010) MicroRNA-141 regulates Smad interacting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells. Digestive diseases and sciences 55: 2365-2372.
61. Park SM, Gaur AB, Lengyel E, Peter ME (2008) The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 22: 894-907.
62. Cheng H, Zhang L, Cogdell DE, Zheng H, Schetter AJ, et al. (2011) Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS ONE 6: e17745.
63. Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, et al. (2009) miR-19 is a key oncogenic component of mir-17-92. Genes Dev 23: 2839-2849.
64. Mavrakis KJ, Wolfe AL, Oricchio E, Palomero T, de Keersmaecker K, et al. (2010) Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 12: 372-379.
65. Luo X, Burwinkel B, Tao S, Brenner H (2011) MicroRNA signatures: novel biomarker for colorectal cancer? Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20: 1272-1286.
66. Lee DY, Deng Z, Wang CH, Yang BB (2007) MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proceedings of the National Academy of Sciences of the United States of America 104: 20350-20355.
67. Schaar DG, Medina DJ, Moore DF, Strair RK, Ting Y (2009) miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation. Experimental hematology 37: 245-255.
68. Yamakuchi M, Lotterman CD, Bao C, Hruban RH, Karim B, et al. (2010) P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 107: 6334-6339.
69. Chen HY, Lin YM, Chung HC, Lang YD, Lin CJ, et al. (2012) miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4. Cancer research 72: 3631-3641.
70. Lindsay MA (2008) microRNAs and the immune response. Trends in immunology 29: 343-351.
71. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, et al. (2008) Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132: 875-886.
72. Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, et al. (2007) MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol 9: 775-787.
73. Christofori G (2006) New signals from the invasive front. Nature 441: 444-450.
74. Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nature reviews Cancer 3: 11-22.
75. Taipale J, Beachy PA (2001) The Hedgehog and Wnt signalling pathways in cancer. Nature 411: 349-354.
76. Morello M, Minciacchi VR, de Candia P, Yang J, Posadas E, et al. (2013) Large oncosomes mediate intercellular transfer of functional microRNA. Cell cycle 12: 3526-3536.
77. Valencia K, Luis-Ravelo D, Bovy N, Anton I, Martinez-Canarias S, et al. (2014) miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization. Molecular oncology 8(3): 689-703.
78. Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, et al. (2013) Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood 121: 984-995.
79. Chen WX, Liu XM, Lv MM, Chen L, Zhao JH, et al. (2014) Exosomes from Drug-Resistant Breast Cancer Cells Transmit Chemoresistance by a Horizontal Transfer of MicroRNAs. PLoS ONE 9: e95240.
80. Liu N, Okamura K, Tyler DM, Phillips MD, Chung WJ, et al. (2008) The evolution and functional diversification of animal microRNA genes. Cell research 18: 985-996.
81. Okamura K, Phillips MD, Tyler DM, Duan H, Chou YT, et al. (2008) The regulatory activity of microRNA∗ species has substantial influence on microRNA and 3′ UTR evolution. Nature structural & molecular biology 15: 354-363.
82. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature reviews Genetics 9: 102-114.
83. Bang C, Batkai S, Dangwal S, Gupta SK, Foinquinos A, et al. (2014) Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. The Journal of clinical investigation 124(5): 2136-46.
84. Nishida N, Nagahara M, Sato T, Mimori K, Sudo T, et al. (2012) Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. Clin Cancer Res 18: 3054-3070.
85. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451: 147-152.
86. Musiyenko A, Bitko V, Barik S (2008) Ectopic expression of miR-126∗, an intronic product of the vascular endothelial EGF-like 7 gene, regulates prostein translation and invasiveness of prostate cancer LNCaP cells. Journal of molecular medicine 86: 313-322.
87. van der Pol E, Boing AN, Harrison P, Sturk A, Nieuwland R (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacological reviews 64: 676-705.
88. Bandres E, Agirre X, Ramirez N, Zarate R, Garcia-Foncillas J (2007) MicroRNAs as cancer players: potential clinical and biological effects. DNA and cell biology 26: 273-282.
89. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 103: 2257-2261.
90. Zhang B, Pan X, Cobb GP, Anderson TA (2007) microRNAs as oncogenes and tumor suppressors. Developmental biology 302: 1-12.
91. Rossi S, Di Narzo AF, Mestdagh P, Jacobs B, Bosman FT, et al. (2012) microRNAs in colon cancer: a roadmap for discovery. FEBS letters 586: 3000-3007.
92. Mazeh H, Mizrahi I, Ilyayev N, Halle D, Brucher B, et al. (2013) The Diagnostic and Prognostic Role of microRNA in Colorectal Cancer - a Comprehensive review. Journal of Cancer 4: 281-295.
93. Schepeler T, Reinert JT, Ostenfeld MS, Christensen LL, Silahtaroglu AN, et al. (2008) Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer research 68: 6416-6424.
94. Xie B, Ding Q, Han H, Wu D (2013) miRCancer: a microRNA-cancer association database constructed by text mining on literature. Bioinformatics 29: 638-644.
95. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, et al. (2005) MicroRNA expression profiles classify human cancers. Nature 435: 834-838.
96. Chen X, Ba Y, Ma L, Cai X, Yin Y, et al. (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell research 18: 997-1006.
97. Dong Y, Wu WK, Wu CW, Sung JJ, Yu J, et al. (2011) MicroRNA dysregulation in colorectal cancer: a clinical perspective. Br J Cancer 104: 893-898.
98. Plaisier CL, Pan M, Baliga NS (2012) A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers. Genome research 22: 2302-2314.
99. Kinet V, Halkein J, Dirkx E, Windt LJ (2013) Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication. Frontiers in genetics 4: 214.
100. Turchinovich A, Weiz L, Langheinz A, Burwinkel B (2011) Characterization of extracellular circulating microRNA. Nucleic acids research 39: 7223-7233.
101. Stoorvogel W (2012) Functional transfer of microRNA by exosomes. Blood 119: 646-648.