MicroRNAs as potential circulating biomarkers of drug-induced liver injury: Key current and future issues for translation to humans

Expert Review of Clinical Pharmacology

Volumn 7, Issue 3, 2014, Pages 349-362

  Hornby, Robert James ^a   Lewis, Philip Starkey ^a   Dear, James ^b,c   Goldring, Chris ^a   Park, Kevin ^a  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b ROYAL INFIRMARY OF EDINBURGH   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Acetaminophen; DILI; Exosome; Hepatocyte; Injury; Liver; MiR 122; MiRNA

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; HEMOGLOBIN; MICRORNA; MICRORNA 1; MICRORNA 122; MICRORNA 16; MICRORNA 192; MICRORNA 193; MICRORNA 238; MICRORNA 24; MICRORNA 323; MICRORNA 39; MICRORNA 48; MICRORNA 54; MICRORNA 675; RNA; UNCLASSIFIED DRUG; UNTRANSLATED RNA; BIOLOGICAL MARKER;

AGE; BIOSENSOR; BLOOD; CALCIUM CELL LEVEL; CEREBROSPINAL FLUID; COMORBIDITY; DRUG OVERDOSE; EUROPE; EXOSOME; HEREDITY; HISTOPATHOLOGY; HUMAN; MICROARRAY ANALYSIS; NONHUMAN; NORTHERN BLOTTING; NUTRITION; PLASMA; POLYPHARMACY; REVERSE TRANSCRIPTION; REVIEW; SERUM; SEX; TOXIC HEPATITIS; UNITED STATES; URINE; ANIMAL; DRUG EFFECTS; DRUG SCREENING; EXOCYTOSIS; GENETIC TRANSCRIPTION; GENETICS; LIVER FUNCTION TEST; SENSITIVITY AND SPECIFICITY;

ANIMALS; BIOLOGICAL MARKERS; DRUG EVALUATION, PRECLINICAL; DRUG-INDUCED LIVER INJURY; EXOCYTOSIS; EXOSOMES; HUMANS; LIVER FUNCTION TESTS; MICRORNAS; SENSITIVITY AND SPECIFICITY; TRANSCRIPTION, GENETIC;

EID: 84898894819     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/17512433.2014.904201     Document Type: Review

References (109)

1. Park BK, Boobis A, Clarke S, et al. Managing the challenge of chemically reactive metabolites in drug development. Nat Rev Drug Discov 2011;1(4):292-306
2. Hussaini SH, Farrington EA. Idiosyncratic drug-induced liver injury: an overview. Expert Opin Drug Saf 2007;1(6):673-84
3. LiverTox. Available from: www.livertox.nih. gov/
4. Murphy SL, Xu J, Kochanek KD. Deaths: final data for 2010. Natl Vital Stat Rep 2013;61:4
5. McShane L. Statistical challenges in the development and evaluation of marker-based clinical tests. BMC Med 2012;1(1):1-5
6. Ozer J, Ratner M, Shaw M, et al. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008;1(3): 194-205
7. Lindblom P, Rafter I, Copley C, et al. Isoforms of alanine aminotransferases in human tissues and serum-Differential tissue expression using novel antibodies. Arch Biochem Biophys 2007;1(1):66-77
8. Zhang Y, Jia Y, Zheng R, et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010;1(12):1830-8
9. Koutedakis Y, Raafat A, Sharp NC, et al. Serum enzyme activities in individuals with different levels of physical fitness. J Sports Med Phys Fitness 1993;33(3):252
10. Kubo M, Yonemoto K, Ninomiya T, et al. Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study. Obesity 2007;1(7):1841-50
11. Lee K-L, Kenney FT. Induction of alanine transaminase by adrenal steroids in cultured hepatoma cells. Biochem Biophys Res Commun 1970;1(2):469-75
12. Danan G, Benichou C. Causality assessment of adverse reactions to drugs - I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;1(11):1323-30
13. Tajiri K, Shimizu Y. Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol 2008;14(44):6774
14. Rochon J, Protiva P, Seeff LB, et al. Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury. Hepatology 2008; 1(4):1175-83
15. Lewis JH, Larrey D, Olsson R, et al. Utility of the Roussel Uclaf Causality Assessment Method (RUCAM) to analyze the hepatic findings in a clinical trial program: evaluation of the direct thrombin inhibitor ximelagatran. Int J Clin Pharmacol Ther 2008;1(7):327-39
16. O'Grady JG, Alexander GJ, Hayllar KM, Williams R. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 1989;1(2):439-45
17. Anand AC, Nightingale P, Neuberger JM. Early indicators of prognosis in fulmitant hepatic failure: an assessment of the King's criteria. J Hepatol 1997;1(1):62-8
18. Shi Q, Hong H, Senior J, Tong W. Biomarkers for drug-induced liver injury. Exp Rev Gastroenterol Hepatol 2010;1(2): 225-34
19. Ohmori S, Shiraki K, Inoue H, et al. Clinical characteristics and prognostic indicators of drug-induced fulminant hepatic failure. Hepatogastroenterology 2003;1(53):1531-4
20. Fabris L, Cadamuro M, Okolicsanyi L. The patient presenting with isolated hyperbilirubinemia. Dig Liver Dis 2009; 1(6):375-81
21. Reust CE. What is the differential diagnosis of an elevated alkaline phosphatase (AP) level in an otherwise asymptomatic patient? Dowden Publishing Corp; 110 Summit Ave, Montvale, NJ 07645-1712, USA: 2001. p. 496-7
22. Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007;1(2): 93-103
23. Wightman B, Bürglin TR, Gatto J, et al. Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development. Genes Dev 1991;1(10):1813-24
24. Arasu P, Wightman B, Ruvkun G. Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. Genes Dev 1991;1(10):1825-33
25. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;1(5):843-54
26. 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 USA 2011;1(12):5003-8
27. Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011;1(16):7223-33
28. Sempere LF, Freemantle S, Pitha-Rowe I, et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 2004;5(3):R13
29. Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 2010;1(1):73-7
30. Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific microRNAs from mouse. Curr Biol 2002; 1(9):735-9
31. Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 1(6956):415-19
32. Bohnsack MT, Czaplinski K, Görlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004; 1(2):185-91
33. Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 2005;1(7051):740-4
34. Cullen BR. Transcription and processing of human microRNA precursors. Mol cell 2004;1(6):861-5
35. Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 2008;1(4):460-71
36. Xu H, He JH, Xiao ZD, et al. Liver-enriched transcription factors regulate microRNA-122 that targets CUTL1 during liver development. Hepatology 2010;1(4): 1431-42
37. Pauli A, Rinn JL, Schier AF. Non-coding RNAs as regulators of embryogenesis. Nat Rev Genet 2011;1(2):136-49
38. Tay Y, Zhang J, Thomson AM, et al. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 2008; 1(7216):1124-8
39. Miyaki S, Sato T, Inoue A, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev 2010;1(11):1173-85
40. Datta J, Kutay H, Nasser MW, et al. Methylation mediated silencing of MicroRNA-1 gene and its role in hepatocellular carcinogenesis. Cancer Res 2008;1(13):5049-58
41. Horie T, Ono K, Nishi H, et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res 2010;1(4):656-64
42. Stern-Ginossar N, Elefant N, Zimmermann A, et al. Host immune system gene targeting by a viral miRNA. Science 2007;1(5836):376-81
43. Pasquinelli AE, Reinhart BJ, Slack F, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000;1(6808):86-9
44. Lee WM. Acetaminophen and the US Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology 2004;1(1):6-9
45. Rumack BH, Matthew H. Acetaminophen poisoning and toxicity. Pediatrics 1975;1(6): 871-6
46. Dear JW, Antoine DJ, Starkey-Lewis P, et al. Letter to the Editor: Early detection of paracetamol toxicity using circulating liver microRNA and markers of cell necrosis. Br J Clin Pharmacol 2013. [Epub ahead of print]
47. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008;1(30): 10513-18
48. miRTarBase: the experimentally validated microRNA-target interactions database. Available from: http://mirtarbase.mbc.nctu. edu.tw/
49. Esau C, Davis S, Murray SF, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006;1(2):87-98
50. Jopling CL, Yi M, Lancaster AM, et al. Modulation of Hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005;1(5740):1577-81
51. Girard M, Jacquemin E, Munnich A, et al. miR-122, a paradigm for the role of microRNAs in the liver. J Hepatol 2008; 1(4):648-56
52. Janssen HLA, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 1(18):1685-94
53. Kutay H, Bai S, Datta J, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem 2006;1(3):671-8
54. Gramantieri L, Ferracin M, Fornari F, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 2007;1(13):6092-9
55. Tsai W-C, Hsu S-D, Hsu C-S, et al. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest 2012;122(8):2884
56. Hsu S-h, Wang B, Kota J, et al. Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. J Clin Invest 2012;122(8):2871
57. Wang K, Zhang S, Marzolf B, et al. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 2009;1(11):4402-7
58. Starkey-Lewis PJ, Dear J, Platt V, et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 2011;1(5):1767-76
59. Antoine DJ, Dear JW, Lewis PS, et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 2013;1(2):777-87
60. Harrill AH, Roach J, Fier I, et al. The effects of heparins on the liver: application of mechanistic serum biomarkers in a randomized study in healthy volunteers. Clin Pharmacol Ther 2012;1(2):214-20
61. Bihrer V, Friedrich-Rust M, Kronenberger B, et al. Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol 2011;1(9):1663-9
62. Xu Y, Xia F, Ma L, et al. MicroRNA-122 sensitizes HCC cancer cells to adriamycin and vincristine through modulating expression of MDR and inducing cell cycle arrest. Cancer Lett 2011; 1(2):160-9
63. Cortez MA, Calin GA. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther 2009;9(6): 703-11
64. Nilsson J, Skog J, Nordstrand A, et al. Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 2009;1(10):1603-7
65. Yang X, Weng Z, Mendrick DL, Shi Q. Circulating extracellular vesicles as a potential source of new biomarkers of drug induced liver injury. Toxicol Lett 2014; 225(3):401-6
66. Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 2011;1(4):423-33
67. Conde-Vancells J, Rodriguez-Suarez E, Gonzalez E, et al. Candidate biomarkers in exosome-like vesicles purified from rat and mouse urine samples. Proteomics Clin Appl 2010;1(4):416-25
68. Taylor DD, Gercel-Taylor C. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects. Br J Cancer 2005;1(2):305-11
69. Ramakrishnaiah V, Thumann C, Fofana I, et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7. 5 cells. Proc Natl Acad Sci USA 2013;1(32):13109-13
70. Pan B-T, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 1983; 1(3):967-78
71. Brooks KB. IgE enhances B cell-derived exosomal induced T cell proliferation. Virginia Commonwealth University Richmond; VA, USA: 1986
72. Sharma K, Karl B, Mathew AV, et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol 2013; 1(11):1901-12
73. Exosome protein, RNA and lipid database. Available from: www.exocarta.org
74. Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 2013;4:2980
75. Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol 2009;1(2):43-51
76. Pisitkun T, Shen R-F, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 2004;1(36):13368-73
77. Taylor DD, Zacharias W, Gercel-Taylor C. Exosome isolation for proteomic analyses and RNA profiling. In: Serum/plasma proteomics. Methods Mol Biol; 2011. p. 235-46
78. Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 1(6):654-9
79. Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008;1(12):5157-66
80. Oosthuyzen W, Sime NEL, Ivy JR, et al. Quantification of human urinary exosomes by nanoparticle tracking analysis. J Physiol 2013;1(23):5833-42
81. Jy W, Horstman LL, Jimenez JJ, Ahn YS. Measuring circulating cell-derived microparticles. J Thromb Haemost 2004; 1(10):1842-3
82. Yano Y, Kambayashi J, Shiba E, et al. The role of protein phosphorylation and cytoskeletal reorganization in microparticle formation from the platelet plasma membrane. Biochem J 1994;299:303-8
83. Boulanger CM, Amabile N, Tedgui A. Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 2006;1(2): 180-6
84. Agouni A, Lagrue-Lak-Hal AH, Ducluzeau PH, et al. Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am J Pathol 2008;1(4):1210-19
85. Sabatier F, Darmon P, Hugel B, et al. Type 1 and type 2 diabetic patients display different patterns of cellular microparticles. Diabetes 2002;1(9):2840-5
86. Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999;1(33):23111-18
87. Witek RP, Yang L, Liu R, et al. Liver Cell- Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells. Gastroenterology 2009;136(1):320-30.e322
88. Chen TS, Lai RC, Lee MM, et al. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res 2010;1(1):215-24
89. Théry C, Boussac M, Véron P, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001;1(12):7309-18
90. Wang K, Zhang S, Weber J, et al. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 2010;1(20):7248-59
91. Bala S, Petrasek J, Mundkur S, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012;1(5):1946-57
92. Schultz NA, Dehlendorff C, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA 2014;1(4):392-404
93. Wang K, Yuan Y, Cho J-H, et al. Comparing the MicroRNA spectrum between serum and plasma. PLoS One 2012;7(7):e41561
94. Yang X, Li Z, Su Z, et al. Urinary microRNAs as noninvasive biomarkers for acetaminophen-induced liver injury. J Postgenom Drug Biomark Develop 2011; 1(101):2153-0769.1000101
95. Duttagupta R, Jiang R, Gollub J, et al. Impact of cellular miRNAs on circulating miRNA biomarker signatures. PLoS One 2011;6(6):e20769
96. Qi R, Weiland M, Gao X-H, et al. Identification of endogenous normalizers for serum MicroRNAs by microarray profiling: U6 small nuclear RNA is not a reliable normalizer. Hepatology 2012;1(5):1640-2
97. Wang G-K, Zhu J-Q, Zhang J-T, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010;1(6):659-66
98. Baraniskin A, Kuhnhenn J, Schlegel U, et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 2011;1(11):3140-6
99. Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 2010;1(4):298-301
100. Shen W, Deng H, Ren Y, Gao Z. A real-time colorimetric assay for label-free detection of microRNAs down to sub-femtomolar levels. Chem Commun 2013;49(43):4959-61
101. Cissell KA, Rahimi Y, Shrestha S, et al. Bioluminescence-based detection of microRNA, miR21 in breast cancer cells. Anal Chem 2008;1(7):2319-25
102. Zhang G-J, Chua JH, Chee R-E, et al. Label-free direct detection of MiRNAs with silicon nanowire biosensors. Biosens Bioelectron 2009;1(8):2504-8
103. Jiang L, Duan D, Shen Y, Li J. Direct microRNA detection with universal tagged probe and time-resolved fluorescence technology. Biosens Bioelectron 2012;1(1): 291-5
104. Broyles D, Cissell K, Kumar M, Deo S. Solution-phase detection of dual microRNA biomarkers in serum. Anal Bioanal Chem 2012;1(1):543-50
105. Mahn R, Heukamp LC, Rogenhofer S, et al. Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology 2011;77(5):1265. e9-16
106. Meder B, Keller A, Vogel B, et al. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol 2011;1(1):13-23
107. Chen S, Xuan J, Guo L. microRNAs in drug-induced liver toxicity. In: Sahu SC, editor. microRNAs in Toxicology and Medicine. John Wiley & Sons Inc; NY, USA: 2013. p. 33
108. Wang F, Zheng Z, Guo J, Ding X. Correlation and quantitation of microRNA aberrant expression in tissues and sera from patients with breast tumor. Gynecol Oncol 2010;1(3):586-93
109. Wang G, Chan ES-Y, Kwan BC-H, et al. Expression of microRNAs in the urine of patients with bladder cancer. Clin Genitourin Cancer 2012;1(2):106-13