Circulating RNA: looking at the liver through a frosted glass

References

• Abdalla MA, Haj-Ahmad Y. (2012). Promising urinary protein biomarkers for the early detection of hepatocellular carcinoma among high-risk hepatitis C virus Egyptian patients. J Cancer 3:390–403
   PubMed Web of Science ®Google Scholar
• Almqvist N, Lonnqvist A, Hultkrantz S, et al. (2008). Serum-derived exosomes from antigen-fed mice prevent allergic sensitization in a model of allergic asthma. Immunology 125:21–7
   PubMed Web of Science ®Google Scholar
• Ambros V. (2004). The functions of animal microRNAs. Nature 431:350–5
   PubMed Web of Science ®Google Scholar
• Anadol E, Schierwagen R, Elfimova N, et al. (2015). Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients. Hepatology 61:46–55
   PubMed Web of Science ®Google Scholar
• Andersson P, Gidlof O, Braun OO, et al. (2012). Plasma levels of liver-specific mir-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia. Shock 37:234–8
   PubMed Web of Science ®Google Scholar
• Arataki K, Hayes CN, Akamatsu S, et al. (2013). Circulating microRNA-22 correlates with microRNA-122 and represents viral replication and liver injury in patients with chronic hepatitis B. J Med Virol 85:789–98
   PubMed Web of Science ®Google Scholar
• Arroyo JD, Chevillet JR, Kroh EM, et al. (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 108:5003–8
   PubMed Web of Science ®Google Scholar
• Bala S, Petrasek J, Mundkur S, et al. (2012a). Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56:1946–57
   PubMed Web of Science ®Google Scholar
• Bala S, Tilahun Y, Taha O, et al. (2012b). Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection. J Translational Med 10:151
   PubMed Web of Science ®Google Scholar
• Bedossa P, Dargere D, Paradis V. (2003). Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 38:1449–57
   PubMed Web of Science ®Google Scholar
• Bertoletti A, Maini MK, Ferrari C. (2010). The host-pathogen interaction during hbv infection: immunological controversies. Antiviral Therapy 15:15–24
   PubMed Web of Science ®Google Scholar
• Bihrer V, Friedrich-Rust M, Kronenberger B, et al. (2011). Serum mir-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol 106:1663–9
   PubMed Web of Science ®Google Scholar
• Bonner C, Nyhan KC, Bacon S, et al. (2013). Identification of circulating microRNAs in HNF1a-mody carriers. Diabetologia 56:1743–51
   PubMed Web of Science ®Google Scholar
• Borel F, Konstantinova P, Jansen PL. (2012). Diagnostic and therapeutic potential of mirna signatures in patients with hepatocellular carcinoma. J Hepatol 56:1371–83
   PubMed Web of Science ®Google Scholar
• Bravo AA, Sheth SG, Chopra S. (2001). Liver biopsy. New Eng J Med 344:495–500
   PubMed Web of Science ®Google Scholar
• Bulera SJ, Eddy SM, Ferguson E, et al. (2001). RNA expression in the early characterization of hepatotoxicants in wistar rats by high-density DNA microarrays. Hepatology 33:1239–58
   PubMed Web of Science ®Google Scholar
• Caby MP, Lankar D, Vincendeau-Scherrer C, et al. (2005). Exosomal-like vesicles are present in human blood plasma. Int Immunol 17:879–87
   PubMed Web of Science ®Google Scholar
• Cermelli S, Ruggieri A, Marrero JA, et al. (2011). Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 6:e23937
   PubMed Web of Science ®Google Scholar
• Cocucci E, Racchetti G, Meldolesi J. (2009). Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51
   PubMed Web of Science ®Google Scholar
• Colombo M, Sangiovanni A. (2003). Etiology, natural history and treatment of hepatocellular carcinoma. Antiviral Res 60:145–50
   PubMed Web of Science ®Google Scholar
• Conde-Vancells J, Rodriguez-Suarez E, Embade N, et al. (2008). Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 7:5157–66
   PubMed Web of Science ®Google Scholar
• Cook NL, Pereira TN, Lewindon PJ, et al. (2015). Circulating microRNAs as noninvasive diagnostic biomarkers of liver disease in children with cystic fibrosis. J Pediatric Gastroenterol Nutr 60:247–54
   PubMed Web of Science ®Google Scholar
• Coulouarn C, Factor VM, Andersen JB, et al. (2009). Loss of mir-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28:3526–36
   PubMed Web of Science ®Google Scholar
• Croce CM. (2009). Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 10:704–14
   PubMed Web of Science ®Google Scholar
• Csak T, Bala S, Lippai D, et al. (2015). MicroRNA-122 regulates hypoxia-inducible factor-1 and vimentin in hepatocytes and correlates with fibrosis in diet-induced steatohepatitis. Liver Int 35:532–41
   PubMed Web of Science ®Google Scholar
• Chan JA, Krichevsky AM, Kosik KS. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–33
   PubMed Web of Science ®Google Scholar
• Chan RW, Wong J, Chan HL, et al. (2010). Aberrant concentrations of liver-derived plasma albumin mrna in liver pathologies. Clin Chem 56:82–9
   PubMed Web of Science ®Google Scholar
• Chan RW, Wong J, Lai PB, et al. (2013). The potential clinical utility of serial plasma albumin mRNA monitoring for the post-liver transplantation management. Clin Biochem 46:1313–19
   PubMed Web of Science ®Google Scholar
• Chang J, Nicolas E, Marks D, et al. (2004). Mir-122, a mammalian liver-specific microRNA, is processed from HCR mRNA and may downregulate the high affinity cationic amino acid transporter cat-1. RNA Biol 1:106–13
   PubMedGoogle Scholar
• Chen CZ, Li L, Lodish HF, Bartel DP. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–6
   PubMed Web of Science ®Google Scholar
• Chen L, Charrier A, Zhou Y, et al. (2014). Epigenetic regulation of connective tissue growth factor by microRNA-214 delivery in exosomes from mouse or human hepatic stellate cells. Hepatology 59:1118–29
   PubMed Web of Science ®Google Scholar
• Chen X, Ba Y, Ma L, et al. (2008). Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006
   PubMed Web of Science ®Google Scholar
• Chen XQ, Bonnefoi H, Pelte MF, et al. (2000). Telomerase RNA as a detection marker in the serum of breast cancer patients. Clin Cancer Res 6:3823–6
   PubMed Web of Science ®Google Scholar
• Chen Y, Shen A, Rider PJ, et al. (2011). A liver-specific microRNA binds to a highly conserved rna sequence of hepatitis b virus and negatively regulates viral gene expression and replication. FASEB J 25:4511–21
   PubMed Web of Science ®Google Scholar
• Day CP. (2011). Non-alcoholic fatty liver disease: a massive problem. Clin Med 11:176–8
   PubMed Web of Science ®Google Scholar
• Dubin PH, Yuan H, Devine RK, et al.; Acute Liver Failure Study Group. (2014). Micro-RNA-122 levels in acute liver failure and chronic hepatitis C. J Med Virol 86:1507–14
   PubMed Web of Science ®Google Scholar
• Elfimova N, Schlattjan M, Sowa JP, et al. (2012). Circulating microRNAs: promising candidates serving as novel biomarkers of acute hepatitis. Front Physiol 3:476
   PubMed Web of Science ®Google Scholar
• Enache LS, Enache EL, Ramiere C, et al. (2014). Circulating RNA molecules as biomarkers in liver disease. Int J Mol Sci 15:17644–66
   PubMed Web of Science ®Google Scholar
• Esau C, Davis S, Murray SF, et al. (2006). Mir-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98
   PubMed Web of Science ®Google Scholar
• Etheridge A, Lee I, Hood L, et al. (2011). Extracellular microRNA: a new source of biomarkers. Mutat Res 717:85–90
   PubMed Web of Science ®Google Scholar
• Farazi PA, DePinho RA. (2006). Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6:674–87
   PubMed Web of Science ®Google Scholar
• Farid WR, Pan Q, van der Meer AJ, et al. (2012). Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transplant 18:290–7
   PubMed Web of Science ®Google Scholar
• Fong MY, Zhou W, Liu L, et al. (2015). Breast-cancer-secreted mir-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 17:183–94
   PubMed Web of Science ®Google Scholar
• Giray BG, Emekdas G, Tezcan S, et al. (2014). Profiles of serum microRNAs; mir-125b-5p and mir223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma. Mol Biol Rep 41:4513–9
   PubMed Web of Science ®Google Scholar
• Gui J, Tian Y, Wen X, et al. (2011). Serum microRNA characterization identifies mir-885-5p as a potential marker for detecting liver pathologies. Clin Sci 120:183–93
   PubMed Web of Science ®Google Scholar
• Halegoua-De Marzio D, Navarro VJ. (2008). Drug-induced hepatotoxicity in humans. Curr Opin Drug Discov Dev 11:53–9
   PubMed Web of Science ®Google Scholar
• Hu Z, Chen X, Zhao Y, et al. (2010). Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 28:1721–6
   PubMed Web of Science ®Google Scholar
• Hunter MP, Ismail N, Zhang X, et al. (2008). Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694
   PubMed Web of Science ®Google Scholar
• Iorio MV, Ferracin M, Liu CG, et al. (2005). microRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–70
   PubMed Web of Science ®Google Scholar
• Jansen C, Eischeid H, Goertzen J, et al. (2014). The role of mirna-34a as a prognostic biomarker for cirrhotic patients with portal hypertension receiving tips. PLoS One 9:e103779
   PubMed Web of Science ®Google Scholar
• Jansen C, Reiberger T, Huang J, et al. (2015). Circulating mirna-122 levels are associated with hepatic necroinflammation and portal hypertension in HIV/HCV coinfection. PLoS One 10:e0116768
   PubMed Web of Science ®Google Scholar
• Ji F, Yang B, Peng X, et al. (2011). Circulating microRNAs in hepatitis b virus-infected patients. J Viral Hepatitis 18:e242–51
   PubMed Web of Science ®Google Scholar
• Johnson PJ. (2001). The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis 5:145–59
   PubMedGoogle Scholar
• Jopling CL, Yi M, Lancaster AM, et al. (2005). Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309:1577–81
   PubMed Web of Science ®Google Scholar
• Koberle V, Kronenberger B, Pleli T, et al. (2013a). Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer 49:3442–9
   PubMed Web of Science ®Google Scholar
• Koberle V, Waidmann O, Kronenberger B, et al. (2013b). Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy. J Viral Hepatitis 20:530–5
   PubMed Web of Science ®Google Scholar
• Kogure T, Lin WL, Yan IK, et al. (2011). Intercellular nanovesicle-mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth. Hepatology 54:1237–48
   PubMed Web of Science ®Google Scholar
• Kopreski MS, Benko FA, Kwak LW, Gocke CD. (1999). Detection of tumor messenger rna in the serum of patients with malignant melanoma. Clin Cancer Res 5:1961–5
   PubMed Web of Science ®Google Scholar
• Kornek M, Lynch M, Mehta SH, et al. (2012). Circulating microparticles as disease-specific biomarkers of severity of inflammation in patients with hepatitis C or nonalcoholic steatohepatitis. Gastroenterology 143:448–58
   PubMed Web of Science ®Google Scholar
• Krutzfeldt J, Rajewsky N, Braich R, et al. (2005). Silencing of microRNAs in vivo with ‘antagomirs'. Nature 438:685–9
   PubMed Web of Science ®Google Scholar
• Kudo Y, Ochi T, Shimada H, et al. (2008). Utility of plasma circulating mRNA as a marker to detect hepatic injury. J Vet Med Sci 70:993–5
   PubMed Web of Science ®Google Scholar
• Kumar S, Chawla YK, Ghosh S, Chakraborti A. (2014). Severity of hepatitis c virus (genotype-3) infection positively correlates with circulating microRNA-122 in patients sera. Dis Markers 2014:435476
   PubMed Web of Science ®Google Scholar
• Ladeiro Y, Couchy G, Balabaud C, et al. (2008). microRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. Hepatology 47:1955–63
   PubMed Web of Science ®Google Scholar
• Lagos-Quintana M, Rauhut R, Yalcin A, et al. (2002). Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–9
   PubMed Web of Science ®Google Scholar
• Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. (2010). Therapeutic silencing of microRNA-122 in primates with chronic hepatitis c virus infection. Science 327:198–201
   PubMed Web of Science ®Google Scholar
• Laterza OF, Scott MG, Garrett-Engele PW, et al. (2013). Circulating mir-122 as a potential biomarker of liver disease. Biomarkers Med 7:205–10
   PubMed Web of Science ®Google Scholar
• Lavanchy D. (2004). Hepatitis b virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepatitis 11:97–107
   PubMed Web of Science ®Google Scholar
• Li J, Wang Y, Yu W, et al. (2011). Expression of serum mir-221 in human hepatocellular carcinoma and its prognostic significance. Biochem Biophys Res Commun 406:70–3
   PubMed Web of Science ®Google Scholar
• Li L, Masica D, Ishida M, et al. (2014). Human bile contains microRNA-laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis. Hepatology 60:896–907
   PubMed Web of Science ®Google Scholar
• Li LM, Hu ZB, Zhou ZX, et al. (2010). Serum microRNA profiles serve as novel biomarkers for hbv infection and diagnosis of hbv-positive hepatocarcinoma. Cancer Res 70:9798–807
   PubMed Web of Science ®Google Scholar
• Liu AM, Yao TJ, Wang W, et al. (2012). Circulating mir-15b and mir-130b in serum as potential markers for detecting hepatocellular carcinoma: a retrospective cohort study. BMJ Open 2:e000825
   PubMed Web of Science ®Google Scholar
• Lo YM, Chiu RW. (2007). Prenatal diagnosis: progress through plasma nucleic acids. Nature Rev Genetics 8:71–7
   PubMed Web of Science ®Google Scholar
• Ma R, Jiang T, Kang X. (2012). Circulating microRNAs in cancer: origin, function and application. J Exp Clin Cancer Res 31:38
   PubMed Web of Science ®Google Scholar
• Markou A, Tsaroucha EG, Kaklamanis L, et al. (2008). Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time rt-pcr. Clinical Chemistry 54:1696–704
   PubMed Web of Science ®Google Scholar
• Matsuzaki K, Murata M, Yoshida K, et al. (2007). Chronic inflammation associated with hepatitis c virus infection perturbs hepatic transforming growth factor beta signaling, promoting cirrhosis and hepatocellular carcinoma. Hepatology 46:48–57
   PubMed Web of Science ®Google Scholar
• McMahon BJ. (2009). The natural history of chronic hepatitis b virus infection. Hepatology 49:S45–55
   PubMed Web of Science ®Google Scholar
• Mitchell PS, Parkin RK, Kroh EM, et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–18
   PubMed Web of Science ®Google Scholar
• Miura N, Kabashima H, Shimizu M, et al. (2008). Clinical impact of serum transforming growth factor-alpha mRNA as a predictive biomarker for the prognosis of fulminant hepatitis. Hepatol Int 2:213–21
   PubMed Web of Science ®Google Scholar
• Miura N, Maeda Y, Kanbe T, et al. (2005). Serum human telomerase reverse transcriptase messenger rna as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res 11:3205–9
   PubMed Web of Science ®Google Scholar
• Miyamoto M, Yanai M, Ookubo S, et al. (2008). Detection of cell-free, liver-specific mrnas in peripheral blood from rats with hepatotoxicity: a potential toxicological biomarker for safety evaluation. Toxicol Sci 106:538–45
   PubMed Web of Science ®Google Scholar
• Moradpour D, Blum HE. (2005). Pathogenesis of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 17:477–83
   PubMed Web of Science ®Google Scholar
• Murakami Y, Toyoda H, Tanahashi T, et al. (2012). Comprehensive miRNA expression analysis in peripheral blood can diagnose liver disease. PLoS One 7:e48366
   PubMed Web of Science ®Google Scholar
• Ng EK, Chong WW, Jin H, et al. (2009). Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58:1375–81
   PubMed Web of Science ®Google Scholar
• Ng EK, Tsui NB, Lam NY, et al. (2002). Presence of filterable and nonfilterable mrna in the plasma of cancer patients and healthy individuals. Clin Chem 48:1212–17
   PubMed Web of Science ®Google Scholar
• Ninomiya M, Kondo Y, Funayama R, et al. (2013). Distinct microRNAs expression profile in primary biliary cirrhosis and evaluation of mir 505-3p and mir197-3p as novel biomarkers. PLoS One 8:e66086
   PubMed Web of Science ®Google Scholar
• Okubo S, Miyamoto M, Takami K, et al. (2013). Identification of novel liver-specific mRNAs in plasma for biomarkers of drug-induced liver injury and quantitative evaluation in rats treated with various hepatotoxic compounds. Toxicol Sci 132:21–31
   PubMed Web of Science ®Google Scholar
• Ozer J, Ratner M, Shaw M, et al. (2008). The current state of serum biomarkers of hepatotoxicity. Toxicology 245:194–205
   PubMed Web of Science ®Google Scholar
• Pais R, Pascale A, Fedchuck L, et al. (2011). Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 35:23–8
   PubMed Web of Science ®Google Scholar
• Parkin DM, Bray F, Ferlay J, Pisani P. (2005). Global cancer statistics, 2002. Cancer J Clinicians 55:74–108
   Web of Science ®Google Scholar
• Pascale A, Pais R, Ratziu V. (2010). An overview of nonalcoholic steatohepatitis: past, present and future directions. J Gastrointestin Liver Dis 19:415–23
   PubMed Web of Science ®Google Scholar
• Peinado H, Aleckovic M, Lavotshkin S, et al. (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through met. Nat Med 18:883–91
   PubMed Web of Science ®Google Scholar
• Pirola CJ, Fernandez Gianotti T, Castano GO, et al. (2015). Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut 64:800–12
   PubMed Web of Science ®Google Scholar
• Povero D, Eguchi A, Li H, et al. (2014). Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease. PLoS One 9:e113651
   PubMed Web of Science ®Google Scholar
• Qi P, Cheng SQ, Wang H, et al. (2011). Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis b virus infection. PLoS One 6:e28486
   PubMed Web of Science ®Google Scholar
• Qiu L, Fan H, Jin W, et al. (2010). Mir-122-induced down-regulation of ho-1 negatively affects mir-122-mediated suppression of HBV. Biochem Biophys Res Commun 398:771–7
   PubMed Web of Science ®Google Scholar
• Qu KZ, Zhang K, Li H, et al. (2011). Circulating microRNAs as biomarkers for hepatocellular carcinoma. J Clin Gastroenterol 45:355–60
   PubMed Web of Science ®Google Scholar
• Roderburg C, Luedde T. (2014). Circulating microRNAs as markers of liver inflammation, fibrosis and cancer. J Hepatol 61:1434–7
   PubMed Web of Science ®Google Scholar
• Roderburg C, Mollnow T, Bongaerts B, et al. (2012). Micro-RNA profiling in human serum reveals compartment-specific roles of mir-571 and mir-652 in liver cirrhosis. PLoS One 7:e32999
   PubMed Web of Science ®Google Scholar
• Royo F, Schlangen K, Palomo L, et al. (2013). Transcriptome of extracellular vesicles released by hepatocytes. PLoS One 8:e68693
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Brunt EM, Kleiner DE, et al. (2011). Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology 54:344–53
   PubMedGoogle Scholar
• Schetter AJ, Leung SY, Sohn JJ, et al. (2008). MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299:425–36
   PubMed Web of Science ®Google Scholar
• Shelke GV, Lasser C, Gho YS, Lotvall J. (2014). Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J Extracellular Vesicles 3:24783
   PubMedGoogle Scholar
• Shen J, Stass SA, Jiang F. (2013a). MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett 329:125–36
   PubMed Web of Science ®Google Scholar
• Shen J, Wang A, Wang Q, et al. (2013b). Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: mir-483-5p as a potential biomarker. Cancer Epidemiol Biomarkers Prevent 22:2364–73
   PubMed Web of Science ®Google Scholar
• Shifeng H, Danni W, Pu C, et al. (2013). Circulating liver-specific mir-122 as a novel potential biomarker for diagnosis of cholestatic liver injury. PLoS One 8:e73133
   PubMed Web of Science ®Google Scholar
• Shigoka M, Tsuchida A, Matsudo T, et al. (2010). Deregulation of mir-92a expression is implicated in hepatocellular carcinoma development. Pathol Int 60:351–7
   PubMed Web of Science ®Google Scholar
• Shrivastava S, Petrone J, Steele R, et al. (2013). Up-regulation of circulating mir-20a is correlated with hepatitis C virus-mediated liver disease progression. Hepatology 58:863–71
   PubMed Web of Science ®Google Scholar
• Shwetha S, Gouthamchandra K, Chandra M, et al. (2013). Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis. Scientific Rep 3:1555
   PubMed Web of Science ®Google Scholar
• Simpson RJ, Lim JW, Moritz RL, Mathivanan S. (2009). Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6:267–83
   PubMed Web of Science ®Google Scholar
• Skog J, Wurdinger T, van Rijn S, et al. (2008). Glioblastoma microvesicles transport rna and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–6
   PubMed Web of Science ®Google Scholar
• Soga K, Watanabe T, Aikawa K, et al. (1998). Serum des-gamma-carboxyprothrombin level by a modified enzyme immunoassay method in hepatocellular carcinoma: clinical significance in small hepatocellular carcinoma. Hepato-Gastroenterology 45:1737–41
   PubMed Web of Science ®Google Scholar
• Starkey Lewis PJ, Dear J, Platt V, et al. (2011). Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 54:1767–76
   PubMed Web of Science ®Google Scholar
• Starley BQ, Calcagno CJ, Harrison SA. (2010). Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 51:1820–32
   PubMed Web of Science ®Google Scholar
• Steel LF, Mattu TS, Mehta A, et al. (2001). A proteomic approach for the discovery of early detection markers of hepatocellular carcinoma. Dis Markers 17:179–89
   PubMed Web of Science ®Google Scholar
• Su YW, Chen X, Jiang ZZ, et al. (2012). A panel of serum microRNAs as specific biomarkers for diagnosis of compound- and herb-induced liver injury in rats. PLoS One 7:e37395
   PubMed Web of Science ®Google Scholar
• Sukata T, Sumida K, Kushida M, et al. (2011). Circulating microRNAs, possible indicators of progress of rat hepatocarcinogenesis from early stages. Toxicol Lett 200:46–52
   PubMed Web of Science ®Google Scholar
• Szabo G, Bala S. (2013). MicroRNAs in liver disease. Nat Rev Gastroenterol Hepatol 10:542–52
   PubMed Web of Science ®Google Scholar
• Thakral S, Ghoshal K. (2015). Mir-122 is a unique molecule with great potential in diagnosis, prognosis of liver disease, and therapy both as miRNA mimic and antimir. Curr Gene Therapy 15:142–50
   PubMed Web of Science ®Google Scholar
• Thorgeirsson SS, Grisham JW. (2002). Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31:339–46
   PubMed Web of Science ®Google Scholar
• Tomimaru Y, Eguchi H, Nagano H, et al. (2012). Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. J Hepato 56:167–75
   PubMed Web of Science ®Google Scholar
• Trebicka J, Anadol E, Elfimova N, et al. (2013). Hepatic and serum levels of mir-122 after chronic hcv-induced fibrosis. J Hepatol 58:234–9
   PubMed Web of Science ®Google Scholar
• Tryndyak VP, Latendresse JR, Montgomery B, et al. (2012). Plasma microRNAs are sensitive indicators of inter-strain differences in the severity of liver injury induced in mice by a choline- and folate-deficient diet. Toxicol Appl Pharmacol 262:52–9
   PubMed Web of Science ®Google Scholar
• Tsai WC, Hsu PW, Lai TC, et al. (2009). MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49:1571–82
   PubMed Web of Science ®Google Scholar
• Waidmann O, Koberle V, Brunner F, et al. (2012). Serum microRNA-122 predicts survival in patients with liver cirrhosis. PLoS One 7:e45652
   PubMed Web of Science ®Google Scholar
• Wang J, Zhang Y, Zhang W, et al. (2012). Association of perfluorooctanoic acid with HDL cholesterol and circulating mir-26b and mir-199-3p in workers of a fluorochemical plant and nearby residents. Environ Sci Technol 46:9274–81
   PubMed Web of Science ®Google Scholar
• Wang K, Yuan Y, Li H, et al. (2013). The spectrum of circulating RNA: a window into systems toxicology. Toxicol Sci 132:478–92
   PubMed Web of Science ®Google Scholar
• Wang K, Zhang S, Marzolf B, et al. (2009). Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 106:4402–7
   PubMed Web of Science ®Google Scholar
• Ward J, Kanchagar C, Veksler-Lublinsky I, et al. (2014). Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc Natl Acad Sci USA 111:12169–74
   PubMed Web of Science ®Google Scholar
• Wetmore BA, Brees DJ, Singh R, et al. (2010). Quantitative analyses and transcriptomic profiling of circulating messenger rnas as biomarkers of rat liver injury. Hepatology 51:2127–39
   PubMed Web of Science ®Google Scholar
• Wieczorek AJ, Rhyner C, Block LH. (1985). Isolation and characterization of an RNA-proteolipid complex associated with the malignant state in humans. Proc Natl Acad Sci USA 82:3455–9
   PubMed Web of Science ®Google Scholar
• Winther TN, Bang-Berthelsen CH, Heiberg IL, et al. (2013a). Differential plasma microRNA profiles in hbeag positive and hbeag negative children with chronic hepatitis B. PLoS One 8:e58236
   PubMed Web of Science ®Google Scholar
• Winther TN, Heiberg IL, Bang-Berthelsen CH, et al. (2013b). Hepatitis b surface antigen quantity positively correlates with plasma levels of microRNAs differentially expressed in immunological phases of chronic hepatitis B in children. PloS One 8:e80384
   PubMed Web of Science ®Google Scholar
• Winther TN, Jacobsen KS, Mirza AH, et al. (2014). Circulating microRNAs in plasma of hepatitis B antigen positive children reveal liver-specific target genes. Int J Hepatol 2014:791045
   PubMedGoogle Scholar
• Xu J, Wu C, Che X, et al. (2011). Circulating microRNAs, mir-21, mir-122, and mir-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinogenesis 50:136–42
   PubMed Web of Science ®Google Scholar
• Yamamoto Y, Kosaka N, Tanaka M, et al. (2009). MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers 14:529–38
   PubMed Web of Science ®Google Scholar
• Yan S, Wang J, Zhang W, Dai J. (2014). Circulating microRNA profiles altered in mice after 28 days exposure to perfluorooctanoic acid. Toxicol Lett 224:24–31
   PubMed Web of Science ®Google Scholar
• Yanez-Mo M, Siljander PR, Andreu Z, et al. (2015). Biological properties of extracellular vesicles and their physiological functions. J Extracellular Vesicles 4:27066
   PubMed Web of Science ®Google Scholar
• Yang S, Wu Y, Wang D, et al. (2012a). Establishment of an experimental method for detecting circulating miRNAs in BDL mice. Clin Exp Med 12:273–7
   PubMed Web of Science ®Google Scholar
• Yang X, Greenhaw J, Shi Q, et al. (2012b). Identification of urinary microRNA profiles in rats that may diagnose hepatotoxicity. Toxicol Sci 125:335–44
   PubMed Web of Science ®Google Scholar
• Zhang H, Li QY, Guo ZZ, et al. (2012). Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B. World J Gastroenterol 18:5188–96
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang Z, Dai F, et al. (2014). Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C. PLoS One 9:e92112
   PubMed Web of Science ®Google Scholar
• Zhang Y, Jia Y, Zheng R, et al. (2010). Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 56:1830–8
   PubMed Web of Science ®Google Scholar
• Zhou J, Yu L, Gao X, et al. (2011). Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol 29:4781–8
   PubMed Web of Science ®Google Scholar
• Zhou M, Gong B, Gu J, Li Z. (2010). EGFRVIII mRNA detection in the serum of patients with hepatocellular carcinoma. Liver 30:925–7
   Google Scholar
• Zinkin NT, Grall F, Bhaskar K, et al. (2008). Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res 14:470–7
   PubMed Web of Science ®Google Scholar