MicroRNAs as signaling mediators and biomarkers of drug-and chemical-induced liver injury

Journal of Clinical Medicine

Volumn 4, Issue 5, 2015, Pages 1063-1078

  McGill, Mitchell R ^a   Jaeschke, Hartmut ^a  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

Author keywords

Acute liver failure; Biomarkers; Drug hepatotoxicity; MicroRNA; MiR 122

Indexed keywords

ALANINE AMINOTRANSFERASE; ARGONAUTE PROTEIN; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; BIOLOGICAL MARKER; CARBON TETRACHLORIDE; CYCLOOXYGENASE 2; ESTRADIOL; MESSENGER RNA; MICRORNA; MICRORNA 122; MICRORNA 125B; MICRORNA 192; MICRORNA 483; MITOCHONDRIAL DNA; PARACETAMOL; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; RNA INDUCED SILENCING COMPLEX; UNCLASSIFIED DRUG; XENOBIOTIC AGENT;

CLINICAL ASSESSMENT; CLINICAL TRIAL (TOPIC); DRUG SAFETY; GENE EXPRESSION; HUMAN; LIVER FIBROSIS; LIVER REGENERATION; MICRORNA EXPRESSION; NONHUMAN; OUTCOME ASSESSMENT; REVIEW; RNA SEQUENCE; SIGNAL TRANSDUCTION; TOXIC HEPATITIS; TOXICITY TESTING;

EID: 84944170000     PISSN: None     EISSN: 20770383     Source Type: Journal    
DOI: 10.3390/jcm4051063     Document Type: Review

References (78)

1. Chalasani, N.; Björnsson, E. Risk factors for idiosyncratic drug-induced liver injury. Gastroenterology 2010, 138, 2246–2259.
2. Lee, W.M. Etiologies of acute liver failure. Semin. Liver Dis. 2008, 28, 142–152.
3. Senior, J.R. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: Current status and challenges. Drug Saf. 2014, 37 (Suppl. 1), S9–S17.
4. United State Food and Drug Administration (US FDA). Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation; United States Food and Drug Administration: Silver Spring, MD, USA, 2009.
5. Ambros, V. microRNAs: Tiny regulators with great potential. Cell 2001, 107, 823–836.
6. Collins, R.E.; Cheng, X. Structural and biochemical advances in mammalian RNAi. J. Cell. Biochem. 2006, 99, 1251–1266.
7. Ha, M.; Kim, V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014, 15, 509–524.
8. Borralho, P.M.; Rodrigues, C.M.; Steer, C.J. Mitochondrial microRNAs and their potential role in cell function. Curr. Pathobiol. Rep. 2014, 2, 123–132.
9. Wheeler, B.M.; Heimberg, A.M.; Moy, V.N.; Sperling, E.A.; Holstein, T.W.; Heber, S.; Peterson, K.J. The deep evolution of metazoan microRNAs. Evol. Dev. 2009, 11, 50–68.
10. Kren, B.T.; Wong, P.Y.; Sarver, A.; Zhang, X.; Zeng, Y.; Steer, C.J. MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biol. 2009, 6, 65–72.
11. Bian, Z.; Li, L.M.; Tang, R.; Hou, D.X.; Chen, X.; Zhang, C.Y.; Zen, K. Identification of mouse liver mitochondria-associated miRNAs and their potential biological functions. Cell Res. 2010, 20, 1076–1078.
12. Esau, C.; Davis, S.; Murray, S.F.; Yu, X.X.; Pandey, S.K.; Pear, M.; Watts, L.; Booten, S.L.; Graham, M.; McKay, R.; et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006, 3, 87–98.
13. Li, S.; Chen, X.; Zhang, H.; Liang, X.; Xiang, Y.; Yu, C.; Zen, K.; Li, Y.; Zhang, C.Y. Differential expression of microRNAs in mouse liver under aberrant energy metabolic status. J. Lipid Res. 2009, 50, 1756–1765.
14. Vincent, R.; Sanyal, A. Recent advances in understanding of NASH: microRNAs as both biochemical markers and players. Curr. Pathobiol. Rep. 2014, 2, 109–115.
15. Soblewski, C.; Calo, N.; Portius, D.; Foti, M. MicroRNAs in fatty liver disease. Semin. Liver Dis. 2015, 35, 12–25.
16. Jopling, C.L.; Yi, M.; Lancaster, A.M.; Lemon, S.M.; Sarnow, P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005, 309, 1577–1581.
17. Murakami, Y.; Aly, H.H.; Tajima, A.; Inoue, I.; Shimotohno, K. Regulation of the hepatitis C virus genome replication by miR-199a. J. Hepatol. 2009, 50, 453–460.
18. Thirion, M.; Ochiya, T. Roles of microRNAs in the hepatitis B virus infection and related diseases. Viruses 2013, 5, 2690–2703.
19. Kanda, T.; Ishibashi, O.; Kawahigashi, Y.; Mishima, T.; Kosuge, T.; Mizuguchi, Y.; Shimizu, T.; Arima, Y.; Yokomuro, S.; Yoshida, H.; et al. Identification of obstructive jaundice-related microRNAs in mouse liver. Hepatogastroenterology 2010, 57, 1013–1023.
20. Dai, B.H.; Geng, L.; Wang, Y.; Sui, C.J.; Cie, F.; Shen, W.F.; Yang, J.M. microRNA-199a-5p protects hepatocytes from bile acid-induced sustained endoplasmic reticulum stress. Cell Death Dis. 2013, 4, doi:10.1038/cddis.2013.134.
21. Fukushima, T.; Hamada, Y.; Yamada, H.; Horii, I. Changes of micro-RNA expression in rat liver treated by acetaminophen or carbon tetrachloride—Regulating role of micro-RNA for RNA expression. J. Toxicol. Sci. 2007, 32, 401–409.
22. Yamaura, Y.; Nakajima, M.; Tastumi, N.; Takagi, S.; Fukami, T.; Tsuneyama, K.; Yokoi, T. Changes in the expression of miRNAs at the pericentral and periportal regions of the rat liver in response to hepatocellular injury: Comparison with the changes in the expression of plasma miRNAs. Toxicology 2014, 322, 89–98.
23. McGill, M.R.; Williams, C.D.; Xie, Y.; Ramachandran, A.; Jaeschke, H. Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol. Appl. Pharmacol. 2012, 264, 387–394.
24. Wang, K.; Zhang, S.; Marzolf, B.; Troisch, P.; Brightman, A.; Hu, Z.; Hood, L.E.; Galas, D.J. Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc. Natl. Acad. Sci. USA 2009, 106, 4402–4407.
25. McGill, M.R.; Yan, H.M.; Ramachandran, A.; Murray, G.J.; Rollins, D.E.; Jaeschke, H. HepaRG cells: A human model to study mechanisms of acetaminophen hepatotoxicity. Hepatology 2011, 53, 974–982.
26. Xie, Y.; McGill, M.R.; Dorko, K.; Kumer, S.C.; Schmitt, T.M.; Forster, J.; Jaeschke, H. Mechanisms of acetaminophen-induced cell death in primary human hepatocytes. Toxicol. Appl. Pharmacol. 2014, 279, 266–274.
27. Lind, R.C.; Gandolfi, A.; Hall, P.D. Age and gender influence halothane-associated hepatotoxicity in strain 13 guinea pigs. Anesthesiology 1989, 71, 878–884.
28. Farrell, G.C.; Frost, L.; Tapner, M.; Field, J.; Weltman, M.; Mahoney, J. Halothane-induced liver injury in guinea-pigs: Importance of cytochrome P450 enzyme activity and hepatic blood flow. J. Gastroenterol. Hepatol. 1996, 11, 594–601.
29. You, Q.; Cheng, L.; Reilly, T.P.; Wegmann, D.; Ju, C. Role of neutrophils in a mouse model of halothane-induced liver injury. Hepatology 2006, 44, 1421–1431.
30. Cheng, L.; You, Q.; Yin, H.; Holt, M.P.; Ju, C. Involvement of natural killer T cells in halothane-induced liver injury in mice. Biochem. Pharmacol. 2010, 80, 255–261.
31. Uetrecht, J.; Naisbitt, D.J. Idiosyncratic adverse drug reactions: Current concepts. Pharmacol. Rev. 2013, 65, 779–808.
32. Endo, S.; Yano, A.; Fukami, T.; Nakajima, M.; Yokoi, T. Involvement of miRNAs in the early phase of halothane-induced liver injury. Toxicology 2014, 319, 75–84.
33. Yoshioka, W.; Higashiyama, W.; Tohyama, C. Involvement of microRNAs in dioxin-induced liver damage in the mouse. Toxicol. Sci. 2011, 122, 457–465.
34. Yang, W.; Lian, J.; Feng, Y.; Srinivas, S.; Guo, Z.; Zhong, H.; Zhuang, Z.; Wang, S. Genome-Wide miRNA-profiling of aflatoxin B1-induced hepatic injury using deep sequencing. Toxicol. Lett. 2014, 226, 140–149.
35. Dippold, R.P.; Vadigepalli, R.; Gonye, G.E.; Hoek, J.B. Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats. Am. J. Gastrointest. Liver Physiol. 2012, 303, G733–G743.
36. Dippold, R.P.; Vadigepalli, R.; Gonye, G.E.; Patra, B.; Hoek, J.B. Chronic ethanol feeding alters miRNA expression dynamics during liver regeneration. Alcohol. Clin. Exp. Res. 2013, 37 (Suppl. 1), E59–E69.
37. Meng, F.; Henson, R.; Wehbe-Jank, H.; Ghoshal, K.; Jacob, S.T.; Patel, T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007, 133, 647–658.
38. Castro, R.E.; Ferreira, D.M.; Zhang, X.; Borralho, P.M.; Sarver, A.L.; Zeng, Y.; Steer, C.J.; Kren, B.T.; Rodrigues C.M. Identification of microRNAs during rat liver regeneration after partial hepatectomy and modulation by ursodeoxycholic acid. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G887–G897.
39. Yoon, S.; Kim, T.H.; Natarajan, A.; Wang, S.S.; Choi, J.; Wu, J.; Zern, M.A.; Venugopal, S.K. Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-alpha-induced apoptosis. Liver Int. 2010, 30, 376–387.
40. Hou, W.; Tian, Q.; Steuerwald, N.M.; Schrum, L.W.; Bonkovsky, H.L. The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes. Biochim. Biophys. Acta 2012, 1819, 1113–1122.
41. Dong, X.; Liu, H.; Chen, F.; Li, D.; Zhao, Y. MiR-214 promotes the alcohol-induced oxidative stress via down-regulation of glutathione reductase and cytochrome P450 oxidoreductase in liver cells. Alcohol. Clin. Exp. Res. 2014, 38, 68–77.
42. Li, X.; Yi, S.; Deng, Y.; Cheng, J.; Wu, X.; Liu, W.; Tai, Y.; Chen, G.; Zhang, Q.; Yang, Y.; et al. MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene. Biochem. Biophys. Res. Commun. 2014, 450, 148–153.
43. Zhang, Y.; Wu, L.; Wang, Y.; Zhang, M.; Li, L.; Zhu, D.; Li, X.; Gu, H.; Zhang, C.Y.; Zen, K.; et al. Protective role of estrogen-induced miRNA-29 expression in carbon tetrachloride-induced mouse liver injury. J. Biol. Chem. 2012, 287, 14851–14862.
44. Zhang, Z.; Zha, Y.; Hu, W.; Huang, Z.; Gao, Z.; Zang, Y.; Chen, J.; Dong, L.; Zhang, J. The autoregulatory feedback loop of microRNA-21/programmed cell death protein 4/activation protein-1 (MiR-21/PDCD4/AP-1) as a driving force for hepatic fibrosis development. J. Biol. Chem. 2013, 288, 37082–37093.
45. Lardizábal, M.N.; Rodríguez, R.E.; Nocito, A.L.; Daniele, S.M.; Palatnik, J.F.; Veggi, L.M. Alteration of the microRNA-122 regulatory network in rat models of hepatotoxicity. Environ. Toxicol. Pharmacol. 2014, 37, 354–364.
46. Bolleyn, J.; Fraczek, J.; Vinken, M.; Lizarraga, D.; Gaj, S.; van Delft, J.H.; Rogiers, V.; Vanhaecke, T. Effect of Trichostatin A on miRNA expression in cultures of primary rat hepatocytes. Toxicol. In Vitro 2011, 25, 1173–1182.
47. Lawrie, C.H.; Gal, S.; Dunlop, H.M.; Pushkaran, B.; Liggins, A.P.; Pulford, K.; Banham, A.H.; Pezzella, F.; Boultwood, J.; Wainscoat, J.S.; et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 2008, 141, 672–675.
48. Zhang, Y.; Jia, Y.; Zheng, R.; Guo, Y.; Wang, Y.; Guo, H.; Fei, M.; Sun, S. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic disorders. Clin. Chem. 2010, 56, 1830–1838.
49. Starkey Lewis, P.J.; Dear, J.; Platt, V.; Simpson, K.J.; Craig, D.G.; Antoine, D.J.; French, N.S.; Dhaun, N.; Webb, D.J.; Costello, E.M.; et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 2011, 54, 1767–1776.
50. Woolbright, B.L.; Antoine, D.J.; Jenkins, R.E.; Bajt, M.L.; Park, B.K.; Jaeschke, H. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice. Toxicol. Appl. Pharmacol. 2013, 273, 524–531.
51. Yang, M.; Antoine, D.J.; Weemhoff, J.L.; Jenkins, R.E.; Farhood, A.; Park, B.K.; Jaeschke, H. Biomarkers distinguish apoptotic and necrotic cell death during hepatic ischemia/reperfusion injury in mice. Liver Transpl. 2014, 20, 1372–1382.
52. Laterza, O.F.; Scott, M.G.; Garrett-Engele, P.W.; Korenblat, K.M.; Lockwood, C.M. Circulating miR-122 as a potential biomarker of liver disease. Biomark. Med. 2013, 7, 205–210.
53. Ward, J.; Kanchagar, C.; Veksler-Lublinsky, I.; Lee, R.C.; McGill, M.R.; Jaeschke, H.; Curry, S.C.; Ambros, V.R. Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc. Natl. Acad. Sci. USA 2014, 111, 12169–12174.
54. McGill, M.R.; Jaeschke, H. Mechanistic biomarkers in acetaminophen-induced hepatotoxicity and acute liver failure: From preclinical models to patients. Expert Opin. Drug Metab. Toxicol. 2014, 10, 1005–1017.
55. Arrese, M.; Eguchi, A.; Feldstein, A.E. Circulating microRNAs: Emerging biomarkers of liver disease. Semin. Liver Dis. 2015, 35, 43–54.
56. Harrill, A.H.; Roach, J.; Fier, I.; Eaddy, J.S.; Kurtz, C.L.; Antoine, D.J.; Spencer, D.M.; Kishimoto, T.K.; Pisetsky, D.S.; Park, B.K.; 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, 92, 214–220.
57. Su, Y.W.; Chen, X.; Jiang, Z.Z.; Wang, T.; Wang, C.; Zhang, Y.; Wen, J.; Xue, M.; Zhu, D.; Zhang, Y.; et al. A panel of serum microRNAs as specific biomarkers for diagnosis of compound-and herb-induced liver injury in rats. PLoS ONE 2012, 7, e37395.
58. Bala, S.; Petrasek, J.; Mundkur, S.; Catalano, D.; Levin, I.; Ward, J.; Alao, H.; Kodys, K.; Szabo, G. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012, 56, 1946–1957.
59. Ward, J.; Bala, S.; Petrasek, J.; Szabo, G. Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study. World J. Gastroenterol. 2012, 18, 2798–27804.
60. Krauskopf, J.; Caiment, F.; Claessen, S.M.; Johnson, K.J.; Warner, R.L.; Schomaker, S.J.; Burt, D.A.; Aubrecht, J.; Kleinjans, J.C. Application of high-throughput sequencing to circulating microRNAs reveals novel biomarkers for drug-induced liver injury. Toxicol. Sci. 2015, 143, 268–276.
61. Yang, X.; Salminen, W.F.; Shi, Q.; Greenhaw, J.; Gill, P.S.; Bhattacharyya, S.; Beger, R.D.; Mendrick, D.L.; Mattes, W.B.; James, L.P.; et al. Potential of extracellular microRNAs as biomarkers of acetaminophen toxicity in childen. Toxicol. Appl. Pharmacol. 2015, doi:10.1016/j.taap.2015.02.013.
62. Dear, J.W.; Antoine, D.J.; Starkey-Lewis, P.; Goldring, C.E.; Park, B.K. Early detection of paracetamol toxicity using circulating liver microRNAs and markers of cell necrosis. Br. J. Clin. Pharmacol. 2014, 77, 904–905.
63. Antoine, D.J.; Dear, J.W.; Lewis, P.S.; Platt, V.; Coyle, J.; Masson, M.; Thanacoody, R.H.; Gray, A.J.; Webb, D.J.; Moggs, J.G.; et al. Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital. Hepatology 2013, 58, 777–787.
64. McGill, M.R.; Staggs, V.S.; Sharpe, M.R.; Lee, W.M.; Jaeschke, H.; Acute Liver Failure Study Group. Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome. Hepatology 2014, 60, 1336–1345.
65. Antoine, D.J.; Jenkins, R.E.; Dear, J.W.; Williams, D.P.; McGill, M.R.; Sharpe, M.R.; Craig, D.G.; Simpson, K.J.; Jaeaschke, H.; Park, B.K.; et al. Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity. J. Hepatol. 2012, 56, 1070–1079.
66. Björnsson, E.; Nordlinder, H.; Olsson, R. Clinical characteristics and prognostic markers in disulfiram-induced liver injury. J. Hepatol. 2006, 44, 791–797.
67. Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659.
68. Van Niel, G.; Porto-Carreiro, I.; Simoes, S.; Raposo, G. Exosomes: A common pathway for a specialized function. J. Biochem. 2006, 140, 13–21.
69. Kowal, J.; Tkach, M.; Théry, C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol. 2014, 29, 116–125.
70. Turchinovich, A.; Weiz, L.; Langheinz, A.; Burwinkel, B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011, 39, 7223–7233.
71. Turchinovich, A.; Weiz, L.; Langheinz, A.; Burwinkel, B. Extracellular miRNAs: The mystery of their origin and function. Trends Biochem. Sci. 2012, 37, 460–465.
72. Royo, F.; Falcon-Perez, J.M. Liver extracellular vesicles in health and disease. J. Extracell. Vesicles 2012, 1, doi:10.3402/jev.v1i0.18825.
73. Wang, K.; Li, H.; Yuan, Y.; Etheridge, A.; Zhou, Y.; Huang, D.; Wilmes, P.; Galas, D. The complex exogenous RNA spectra in human plasma: An interface with human gut biota? PLoS ONE 2012, 7, e51009.
74. Nelson, P.T.; Wang, W.X.; Wilfred, B.R.; Tang, G. Technical variables in high-throughput miRNA expression profiling: Much work remains to be done. Biochim. Biophys. Acta 2008, 1779, 758–765.
75. Chugh, P.; Dittmer, D.P. Potential pitfalls in microRNA profiling. Wiley Interdiscip. Rev. RNA 2012, 3, 601–616.
76. Qi, R.; Weiland, M.; Gao, X.H.; Zhou, L.; Mi, Q.S. Identification of endogenous normalizers for serum microRNAs by microarray profiling: U6 small nuclear RNA is not a reliable normalizer. Hepatology 2012, 55, 1640–1642.
77. Kirschner, M.B.; Kao, S.C.; Edelman, J.J.; Armstrong, N.J.; Vallely, M.P.; van Zandwijk, N.; Reid, G. Haemolysis during sample preparation alters microRNA content of plasma. PLoS ONE 2011, 6, e24145.
78. Kirschner, M.B.; Edelman, J.J.; Kao, S.C.; Vallely, M.P.; van Zandwijk, N.; Reid, G. The impact of hemolysis on cell-fre microRNA biomarkers. Front. Genet. 2013, 4, doi:10.3389/fgene.2013.00094.