microRNA and internal medicine: from pathophysiology to the new diagnostic and therapeutic procedures
Authors:
Jan Novák 1,2; Miroslav Souček 1
Authors‘ workplace:
II. interní klinika LF MU a FN U sv. Anny v Brně
1; Fyziologický ústav LF MU v Brně
2
Published in:
Vnitř Lék 2016; 62(6): 477-485
Category:
Reviews
Overview
microRNAs (abbreviated miRNAs or miRs) represents one of the group of so called small non-coding RNAs which participate in the negative post-transcriptional regulation of gene expression. According to the base complementarity they target molecules of messenger RNAs (mRNAs) which results either in translational blockade or in degradation of target mRNA. One miRNA usually targets more mRNA and one mRNA is usually targeted by more than one miRNA – complicated and interconnected regulatory networks are thus created and their disruption leads to the abnormalities in development or results in the development of diseases. Within the past two decades, novel mechanisms were described that enable us to modulate miRNA levels (either causing upregulation or downregulation) – miRNAs can thus be considered as a novel potential group of therapeutic targets. First clinical trials using the blockade of liver specific miR-122 showed very promising results in the treatment of chronic hepatitis C virus infection. Results of preclinical and animal studies are also promising providing future rationale for the development of new therapeutics for various internal diseases including heart failure, bronchial asthma or inflammatory bowel diseases. Moreover, miRNAs are not only affecting the pathophysiology of internal diseases, but they can also reflect their presence – there is a group of miRNAs called extracellular, or circulating miRNAs, i.e. miRNAs that are present in extracellular space including all known body fluids such as plasma, serum, urine, saliva or sweat. Circulating miRNAs are stable; their levels are constant among the individuals of one species, methods determining their levels are reproducible and last but not least – levels of extracellular miRNAs differ between healthy and diseased individuals. They are released into the circulation either after the cell necrosis or by active transport. Except of being potential novel biomarkers, these miRNAs represent a novel mean of intercellular communication. Their levels thus reflect not only the organ damage but also the changes of the homeostasis during various illnesses. The aim of the current study is to provide the first insight into the miRNA world to clinicians, especially to internal medicine specialists. Using simple examples from clinical praxis or clinical pathophysiology, we are trying to present diagnostic and therapeutic potential that is hidden within these tiny interesting molecules.
Key words:
circulating microRNA – diagnostics – internal diseases – microRNA – therapy
Sources
1. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12(12): 861–874.
2. Alexander RP, Fang G, Rozowsky J et al. Annotating non-coding regions of the genome. Nat Rev Genet 2010; 11(8): 559–571.
3. Sayed D, Abdellatif M. MicroRNAs in development and disease. Physiol Rev 2011; 91(3): 827–887.
4. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281–297.
5. Novák J, Bienertová-Vašků J, Kára T et al. MicroRNAs involved in the lipid metabolism and their possible implications for atherosclerosis development and treatment. Mediators Inflamm 2014; 2014: 275867. Dostupné z DOI: http://dx.doi.org/10.1155/2014/275867.
6. Rayner KJ, Suárez Y, Dávalos A et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science 2010; 328(5985): 1570–1573.
7. Allen RM, Marquart TJ, Albert CJ et al. miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity. EMBO Mol Med 2012; 4(9): 882–895.
8. 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(5): 843–854.
9. Pasquinelli AE, Reinhart BJ, Slack F et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000; 408(6808): 86–89.
10. Yang WJ, Yang DD, Na S et al. Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem 2005; 280(10): 9330–9335.
11. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99(24): 15524–15529.
12. Cimmino A, Calin GA, Fabbri M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102(39): 13944–13949.
13. Calin GA, Sevignani C, Dumitru CD et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101(9): 2999–3004.
14. Slabý O, Svoboda M et al. mikroRNA v onkologii. Galén: Praha 2012. ISBN 978–80–7262–587–1.
15. Ebrahimi A, Sadroddiny E. MicroRNAs in lung diseases: Recent findings and their pathophysiological implications. Pulm Pharmacol Ther 2015; 34: 55–63.
16. Bansal A, Hong X, Lee IH et al. MicroRNA Expression can be a Promising Strategy for the Detection of Barrett’s Esophagus: A Pilot Study. Clin Transl Gastroenterol 2014; 5: e65. Dostupné z DOI: http://dx.doi.org/10.1038/ctg.2014.17.
17. Kalla R, Ventham NT, Kennedy NA et al. MicroRNAs: new players in IBD. Gut 2015; 64(3): 504–517.
18. O’Connell RM, Baltimore D. MicroRNAs and hematopoietic cell development. Curr Top Dev Biol 2012; 99: 145–174.
19. Economou EK, Oikonomou E, Siasos G et al. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis 2015; 241(2): 624–633.
20. Kalozoumi G, Yacoub M, Sanoudou D. MicroRNAs in heart failure: Small molecules with major impact. Glob Cardiol Sci Pract 2014; 2014(2): 79–102. Dostupné z DOI: http://dx.doi.org/10.5339/gcsp.2014.30.
21. Shi L, Liao J, Liu B et al. Mechanisms and therapeutic potential of microRNAs in hypertension. Drug Discov Today 2015; 20(10): 1188–1204.
22. Fu X, Zhou Y, Cheng Z et al. MicroRNAs: Novel Players in Aortic Aneurysm. BioMed Res Int 2015; 2015: 831641. Dostupné z DOI: http://dx.doi.org/10.1155/2015/831641.
23. Price NL, Ramírez CM, Fernández-Hernando C. Relevance of microRNA in metabolic diseases. Crit Rev Clin Lab Sci 2014; 51(6): 305–320.
24. Tang P, Xiong Q, Ge W et al. The role of microRNAs in osteoclasts and osteoporosis. RNA Biol 2014; 11(11): 1355–1363.
25. Trionfini P, Benigni A, Remuzzi G. MicroRNAs in kidney physiology and disease. Nat Rev Nephrol 2015; 11(1): 23–33.
26. Janssen HLA, Reesink HW, Lawitz EJ et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 368(18): 1685–1694.
27. Lambert JLW, Grine L, Van Gele M. microRNAs in psoriasis: leaders or followers? Br J Dermatol 2015; 173(2): 323.
28. van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov 2012; 11(11): 860–872.
29. van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res 2012; 110(3): 496–507.
30. Mitchell PS, Parkin RK, Kroh EM et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30): 10513–10518.
31. Chen X, Ba Y, Ma L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18(10): 997–1006.
32. Gilad S, Meiri E, Yogev Y et al. Serum microRNAs are promising novel biomarkers. PloS One 2008; 3(9): e3148. Dostupné z DOI: http://dx.doi.org/10.1371/journal.pone.0003148.
33. Weber JA, Baxter DH, Zhang S et al. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56(11): 1733–1741.
34. Lagos-Quintana M, Rauhut R, Yalcin A et al. Identification of Tissue-Specific MicroRNAs from Mouse. Curr Biol 2002; 12(9): 735–739.
35. Kinet V, Halkein J, Dirkx E et al. Cardiovascular extracellular microRNAs: emerging diagnostic markers and mechanisms of cell-to-cell RNA communication. Front Genet 2013; 4: 214.
36. Cheng C, Wang Q, You W et al. MiRNAs as biomarkers of myocardial infarction: a meta-analysis. PloS One 2014; 9(2): e88566. Dostupné z DOI: http://dx.doi.org/10.1371/journal.pone.0088566.
37. Figueira MF, Monnerat-Cahli G, Medei E et al. MicroRNAs: potential therapeutic targets in diabetic complications of the cardiovascular and renal systems. Acta Physiol Oxf Engl 2014; 211(3): 491–500.
38. Zampetaki A, Kiechl S, Drozdov I et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 2010; 107(6): 810–817.
39. Erener S, Mojibian M, Fox JK et al. Circulating miR-375 as a biomarker of β-cell death and diabetes in mice. Endocrinology 2013; 154(2): 603–608.
40. Wang M, Huang Y, Liang Z et al. Plasma miRNAs might be promising biomarkers of chronic obstructive pulmonary disease. Clin Respir J 2016; 10(1): 104–111.
41. Zhang R, Niu H, Ban T et al. Elevated plasma microRNA-1 predicts heart failure after acute myocardial infarction. Int J Cardiol 2013; 166(1): 259–260.
42. Zhao Q, Cao J, Wu YC et al. Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers. Am J Cancer Res 2015; 5(5): 1692–1705.
43. Zernecke A, Bidzhekov K, Noels H et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2009; 2: ra81. Dostupné z DOI: <http://doi: 10.1126/scisignal.2000610>.
44. Li J, Zhang Y, Liu Y et al. Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis. J Biol Chem 2013; 288(32): 23586–23596.
45. Liu Y, Zhao L, Li D et al. Microvesicle-delivery miR-150 promotes tumorigenesis by up-regulating VEGF, and the neutralization of miR-150 attenuate tumor development. Protein Cell 2013; 4(12): 932–941.
46. Wagner J, Riwanto M, Besler C et al. Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs. Arterioscler Thromb Vasc Biol 2013; 33(6): 1392–1400.
47. Seeger T, Fischer A, Muhly-Reinholz M et al. Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice. Obes Silver Spring Md 2014; 22(11): 2352–2360.
48. Rayner KJ, Esau CC, Hussain FN et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 2011; 478(7369): 404–407.
49. Najafi-Shoushtari SH, Kristo F, Li Y et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 2010; 328(5985): 1566–1569.
50. Boon RA, Seeger T, Heydt S et al. MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 2011; 109(10): 1115–1119.
51. Maegdefessel L, Azuma J, Toh R et al. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J Clin Invest 2012; 122(2): 497–506.
52. Hullinger TG, Montgomery RL, Seto AG et al. Inhibition of miR-15 protects against cardiac ischemic injury. Circ Res 2012; 110(1): 71–81.
53. Porrello ER, Johnson BA, Aurora AB et al. MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circ Res 2011; 109(6): 670–679.
54. Montgomery RL, Hullinger TG, Semus HM et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation 2011; 124(14): 1537–1547.
55. Caruso P, Dempsie Y, Stevens HC et al. A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples. Circ Res 2012; 111(3): 290–300.
56. Sharma A, Kumar M, Ahmad T et al. Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model. J Appl Physiol (1985) 2012; 113(3): 459–464.
57. Huang Z, Shi T, Zhou Q et al. miR-141 Regulates colonic leucocytic trafficking by targeting CXCL12β during murine colitis and human Crohn’s disease. Gut 2014; 63(8): 1247–1257.
58. Singh UP, Murphy AE, Enos RT et al. miR-155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses. Immunology 2014; 143(3): 478–489.
59. Tijsen AJ, Creemers EE, Moerland PD et al. MiR423–5p as a circulating biomarker for heart failure. Circ Res 2010; 106(6): 1035–1039.
60. Liu Z, Zhou C, Liu Y et al. The expression levels of plasma micoRNAs in atrial fibrillation patients. PloS One 2012; 7(9): e44906. Dostupné z DOI: http://dx.doi.org/10.1371/journal.pone.0044906.
61. Kessler T, Erdmann J, Vilne B et al. Serum microRNA-1233 is a specific biomarker for diagnosing acute pulmonary embolism. J Transl Med 2016; 14(1): 120.
62. Yang Q, Jia C, Wang P et al. MicroRNA-505 identified from patients with essential hypertension impairs endothelial cell migration and tube formation. Int J Cardiol 2014; 177(3): 925–934.
63. Li S, Zhu J, Zhang W et al. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation 2011; 124(2): 175–184.
64. Wang X, Sundquist K, Elf JL et al. Diagnostic potential of plasma microRNA signatures in patients with deep-vein thrombosis. Thromb Haemost 2016; 116(2). [Epub ahead of print].
65. Zhang W, Shang T, Huang C et al. Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm. Clin Biochem 2015; 48(15): 988–992.
66. Wang M, Huang Y, Liang Z et al. Plasma miRNAs might be promising biomarkers of chronic obstructive pulmonary disease. Clin Respir J 2016; 10(1): 104–111.
67. Li P, Li J, Chen T et al. Expression analysis of serum microRNAs in idiopathic pulmonary fibrosis. Int J Mol Med 2014; 33(6): 1554–1562.
68. Yang G, Yang L, Wang W et al. Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fibrosis disease progression. Gene 2015; 562(1): 138–144.
69. Jazwa A, Kasper L, Bak M et al. Differential Inflammatory MicroRNA and Cytokine Expression in Pulmonary Sarcoidosis. Arch Immunol Ther Exp (Warsz) 2014; 63(2): 139–146.
70. Schaefer JS, Attumi T, Opekun AR et al. MicroRNA signatures differentiate Crohn’s disease from ulcerative colitis. BMC Immunol 2015; 16: 5. Dostupné z DOI: <http://dx.doi.org/10.1186/s12865–015–0069–0>.
71. Krissansen GW, Yang Y, McQueen FMM et al. Overexpression of miR-595 and miR-1246 in the Sera of Patients with Active Forms of Inflammatory Bowel Disease. Inflamm Bowel Dis 2015; 21(3): 520–530.
72. Szeto CC. Urine miRNA in nephrotic syndrome. Clin Chim Acta 2014; 436: 308–313.
73. Bernuzzi F, Marabita F, Lleo A et al. Serum micrornas as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Clin Exp Immunol 2016; 185(1): 61–71.
74. Roderburg C, Benz F, Vargas Cardenas D et al. Elevated miR-122 serum levels are an independent marker of liver injury in inflammatory diseases. Liver Int 2015; 35(4): 1172–1184.
75. McCrae JC, Sharkey N, Webb DJ et al. Ethanol consumption produces a small increase in circulating miR-122 in healthy individuals. Clin Toxicol Phila 2016; 54(1): 53–55.
76. Zampetaki A, Willeit P, Burr S et al. Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes. Diabetes 2016; 65(1): 216–227.
77. Wang C, Wan S, Yang T et al. Increased serum microRNAs are closely associated with the presence of microvascular complications in type 2 diabetes mellitus. Sci Rep 2016; 6: 20032. Dostupné z DOI: http://dx.doi.org/10.1038/srep20032.
78. Raffort J, Hinault C, Dumortier O et al. Circulating microRNAs and diabetes: potential applications in medical practice. Diabetologia 2015; 58(9): 1978–1992.
79. Stypińska B, Paradowska-Gorycka A Cytokines and MicroRNAs as Candidate Biomarkers for Systemic Lupus Erythematosus. Int J Mol Sci 2015; 16(10): 24194–24218.
80. Wang W, Zhang Y, Zhu B et al. Plasma microRNA expression profiles in Chinese patients with rheumatoid arthritis. Oncotarget 2015; 6(40): 42557–42568.
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Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2016 Issue 6
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