{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:14:16Z","timestamp":1791227656997,"version":"4.1.0"},"reference-count":97,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T00:00:00Z","timestamp":1412035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver disease is a major cause of morbidity and mortality worldwide. As in other fields of medicine, there is a stringent need for non-invasive markers to improve patient diagnostics, monitoring and prognostic ability in liver pathology. Cell-free circulating RNA molecules have been recently acknowledged as an important source of potential medical biomarkers. However, many aspects related to the biology of these molecules remain to be elucidated. In this review, we summarize current concepts related to the origin, transportation and possible functions of cell-free RNA. We outline current development of extracellular RNA-based biomarkers in the main forms of non-inherited liver disease: chronic viral hepatitis, hepatocellular carcinoma, non-alcoholic fatty liver, hepato-toxicity, and liver transplantation. Despite recent technological advances, the lack of standardization in the assessment of these markers makes their adoption into clinical practice difficult. We thus finally review the main factors influencing quantification of circulating RNA. These factors should be considered in the reporting and interpretation of current findings, as well as in the proper planning of future studies, to improve reliability and reproducibility of results.<\/jats:p>","DOI":"10.3390\/ijms151017644","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T10:57:30Z","timestamp":1412074650000},"page":"17644-17666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Circulating RNA Molecules as Biomarkers in Liver Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Liviu","family":"Enache","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Lyon F-69008, France"},{"name":"University of Medicine and Pharmacy Tirgu Mures, 38 Gh. Marinescu st., Tirgu Mures 540142, Romania"},{"name":"Emergency County Clinical Hospital, 50 Gh. Marinescu st.,  Tirgu Mures 540136, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Enache","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy Tirgu Mures, 38 Gh. Marinescu st., Tirgu Mures 540142, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Rami\u00e8re","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Lyon F-69008, France"},{"name":"Inserm U1111, 21 Avenue Tony Garnier, Lyon F-69007, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Universit\u00e9 de Lyon,  21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 15 parvis Ren\u00e9 Descartes, BP 7000 69342 Lyon Cedex 07, France"},{"name":"CNRS, UMR5308, 21 avenue Tony Garnier, 69365 Lyon Cedex 07, France"},{"name":"Hospices Civils de Lyon, H\u00f4pital de la Croix Rousse, Laboratoire de Virologie, Lyon F-69004, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Diaz","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Lyon F-69008, France"},{"name":"Inserm U1111, 21 Avenue Tony Garnier, Lyon F-69007, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Universit\u00e9 de Lyon,  21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 15 parvis Ren\u00e9 Descartes, BP 7000 69342 Lyon Cedex 07, France"},{"name":"CNRS, UMR5308, 21 avenue Tony Garnier, 69365 Lyon Cedex 07, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia","family":"Bancu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy Tirgu Mures, 38 Gh. Marinescu st., Tirgu Mures 540142, Romania"},{"name":"Emergency County Clinical Hospital, 50 Gh. Marinescu st.,  Tirgu Mures 540136, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Sin","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy Tirgu Mures, 38 Gh. Marinescu st., Tirgu Mures 540142, Romania"},{"name":"Emergency County Clinical Hospital, 50 Gh. Marinescu st.,  Tirgu Mures 540136, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Andr\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lyon, Universit\u00e9 Lyon 1, Lyon F-69008, France"},{"name":"Inserm U1111, 21 Avenue Tony Garnier, Lyon F-69007, France"},{"name":"CIRI, Centre International de Recherche en Infectiologie, Universit\u00e9 de Lyon,  21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, 15 parvis Ren\u00e9 Descartes, BP 7000 69342 Lyon Cedex 07, France"},{"name":"CNRS, UMR5308, 21 avenue Tony Garnier, 69365 Lyon Cedex 07, France"},{"name":"Hospices Civils de Lyon, H\u00f4pital de la Croix Rousse, Laboratoire de Virologie, Lyon F-69004, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2012). EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J. Hepatol., 57, 167\u2013185.","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"ref_2","unstructured":"EASL Recommendations on Treatment of Hepatitis C. Available online:http:\/\/files.easl.eu\/easl-recommendations-on-treatment-of-hepatitis-C.pdf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2011.12.061","article-title":"Epidemiology of viral hepatitis and hepatocellular carcinoma","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver, and European Organisation for Research and Treatment of Cancer (2012). EASL\u2013EORTC Clinical Practice Guidelines: management of hepatocellular carcinoma. J. Hepatol., 56, 908\u2013943.","DOI":"10.1016\/j.jhep.2011.12.001"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/00313020701230831","article-title":"Circulating nucleic acids in plasma\/serum","volume":"39","author":"Tsang","year":"2007","journal-title":"Pathology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1373\/clinchem.2010.147405","article-title":"The microRNA spectrum in 12 body fluids","volume":"56","author":"Weber","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1093\/clinchem\/48.10.1647","article-title":"Stability of endogenous and added RNA in blood specimens, serum, and plasma","volume":"48","author":"Tsui","year":"2002","journal-title":"Clin. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1373\/clinchem.2003.028506","article-title":"Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics","volume":"50","author":"Raja","year":"2004","journal-title":"Clin. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/hep.23574","article-title":"Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury","volume":"51","author":"Wetmore","year":"2010","journal-title":"Hepatol. Baltim. Md."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1006\/excr.2000.5027","article-title":"Segregation of RNA and separate packaging of DNA and RNA in apoptotic bodies during apoptosis","volume":"260","author":"Halicka","year":"2000","journal-title":"Exp. Cell Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tcb.2008.11.003","article-title":"Shedding microvesicles: Artefacts no more","volume":"19","author":"Cocucci","year":"2009","journal-title":"Trends Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1261\/rna.755908","article-title":"Extracellular plasma RNA from colon cancer patients is confined in a vesicle-like structure and is mRNA-enriched","volume":"14","author":"Silva","year":"2008","journal-title":"RNA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bolukbasi, M.F., Mizrak, A., Ozdener, G.B., Madlener, S., Str\u00f6bel, T., Erkan, E.P., Fan, J.-B., Breakefield, X.O., and Saydam, O. (2012). miR-1289 and \u201cZipcode\u201d-like sequence enrich mRNAs in microvesicles. Mol. Ther. Nucleic Acids, 1.","DOI":"10.1038\/mtna.2011.2"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1073\/pnas.1019055108","article-title":"Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma","volume":"108","author":"Arroyo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.1093\/nar\/gkr254","article-title":"Characterization of extracellular circulating microRNA","volume":"39","author":"Turchinovich","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.4161\/rna.21083","article-title":"Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma","volume":"9","author":"Turchinovich","year":"2012","journal-title":"RNA Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/hep.25873","article-title":"Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases","volume":"56","author":"Bala","year":"2012","journal-title":"Hepatol. Baltim. Md."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ncb2210","article-title":"MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins","volume":"13","author":"Vickers","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"L\u00e4sser, C., Alikhani, V.S., Ekstr\u00f6m, K., Eldh, M., Paredes, P.T., Bossios, A., Sj\u00f6strand, M., Gabrielsson, S., L\u00f6tvall, J., and Valadi, H. (2011). Human saliva, plasma and breast milk exosomes contain RNA: Uptake by macrophages. J. Transl. Med., 9.","DOI":"10.1186\/1479-5876-9-9"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-Mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1182\/blood-2007-03-078709","article-title":"Endothelial progenitor cell\u2013derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA","volume":"110","author":"Deregibus","year":"2007","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e34653","DOI":"10.1371\/journal.pone.0034653","article-title":"Cardiomyocyte microvesicles contain DNA\/RNA and convey biological messages to target cells","volume":"7","author":"Hellman","year":"2012","journal-title":"PLoS One"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/hep.24504","article-title":"Intercellular nanovesicle-mediated microRNA transfer: A mechanism of environmental modulation of hepatocellular cancer cell growth","volume":"54","author":"Kogure","year":"2011","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1002\/stem.1161","article-title":"Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor MicroRNAs","volume":"30","author":"Fonsato","year":"2012","journal-title":"Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1136\/gutjnl-2011-300449","article-title":"Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi)","volume":"61","author":"Pan","year":"2012","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1373\/clinchem.2009.131797","article-title":"Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury","volume":"55","author":"Laterza","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mrfmmm.2011.03.004","article-title":"Extracellular microRNA: A new source of biomarkers","volume":"717","author":"Etheridge","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/toxsci\/kfn188","article-title":"Detection of cell-free, liver-specific mRNAs in peripheral blood from rats with hepatotoxicity: A potential toxicological biomarker for safety evaluation","volume":"106","author":"Miyamoto","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/toxsci\/kfs340","article-title":"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","volume":"132","author":"Okubo","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1073\/pnas.0813371106","article-title":"Circulating microRNAs, potential biomarkers for drug-induced liver injury","volume":"106","author":"Wang","year":"2009","journal-title":"Proc. Natl. Acad. Sci.USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1002\/hep.24538","article-title":"Circulating microRNAs as potential markers of human drug-induced liver injury","volume":"54","author":"Dear","year":"2011","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1373\/clinchem.2009.133355","article-title":"Aberrant concentrations of liver-derived plasma albumin mRNA in liver pathologies","volume":"56","author":"Chan","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_33","first-page":"183","article-title":"Serum microRNA characterization identifies miR-885\u20135p as a potential marker for detecting liver pathologies","volume":"120","author":"Gui","year":"2011","journal-title":"Clin. Sci. Lond. Engl. 1979"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e48366","DOI":"10.1371\/journal.pone.0048366","article-title":"Comprehensive miRNA expression analysis in peripheral blood can diagnose liver disease","volume":"7","author":"Murakami","year":"2012","journal-title":"PLoS One"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9798","DOI":"10.1158\/0008-5472.CAN-10-1001","article-title":"Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma","volume":"70","author":"Li","year":"2010","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23937","DOI":"10.1371\/journal.pone.0023937","article-title":"Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease","volume":"6","author":"Cermelli","year":"2011","journal-title":"PLoS One"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e32999","DOI":"10.1371\/journal.pone.0032999","article-title":"Micro-RNA profiling in human serum reveals compartment-specific roles of miR-571 and miR-652 in liver cirrhosis","volume":"7","author":"Roderburg","year":"2012","journal-title":"PLoS One"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/ajg.2011.161","article-title":"Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection","volume":"106","author":"Bihrer","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jhep.2012.10.015","article-title":"Hepatic and serum levels of miR-122 after chronic HCV induced fibrosis","volume":"58","author":"Trebicka","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1373\/clinchem.2010.147850","article-title":"Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases","volume":"56","author":"Zhang","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e92112","DOI":"10.1371\/journal.pone.0092112","article-title":"Comparison of circulating, hepatocyte specific messenger RNA and microRNA as biomarkers for chronic hepatitis B and C","volume":"9","author":"Zhang","year":"2014","journal-title":"PLoS One"},{"key":"ref_42","first-page":"5188","article-title":"Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B","volume":"18","author":"Zhang","year":"2012","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/mc.20712","article-title":"Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis","volume":"50","author":"Xu","year":"2011","journal-title":"Mol. Carcinog."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e58236","DOI":"10.1371\/journal.pone.0058236","article-title":"Differential plasma microRNA profiles in HBeAg positive and HBeAg negative children with chronic hepatitis B","volume":"8","author":"Winther","year":"2013","journal-title":"PLoS One"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e80384","DOI":"10.1371\/journal.pone.0080384","article-title":"Hepatitis B surface antigen quantity positively correlates with plasma levels of microRNAs differentially expressed in immunological phases of chronic hepatitis B in children","volume":"8","author":"Winther","year":"2013","journal-title":"PLoS One"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/01.tp.0000298003.88530.11","article-title":"Albumin mRNA in plasma predicts post-transplant recurrence of patients with hepatocellular carcinoma","volume":"85","author":"Cheung","year":"2008","journal-title":"Transplant"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhep.2011.04.026","article-title":"Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma","volume":"56","author":"Tomimaru","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e28486","DOI":"10.1371\/journal.pone.0028486","article-title":"Serum MicroRNAs as biomarkers for hepatocellular carcinoma in chinese patients with chronic hepatitis B virus infection","volume":"6","author":"Qi","year":"2011","journal-title":"PLoS One"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1200\/JCO.2011.38.2697","article-title":"Plasma MicroRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma","volume":"29","author":"Zhou","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.clinbiochem.2013.04.022","article-title":"The potential clinical utility of serial plasma albumin mRNA monitoring for the post-liver transplantation management","volume":"46","author":"Chan","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/lt.22438","article-title":"Hepatocyte-Derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation","volume":"18","author":"Farid","year":"2012","journal-title":"Liver Transpl."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Pirola, C.J., Gianotti, T.F., Casta\u00f1o, G.O., Mallardi, P., Martino, J.S., Ledesma, M.M.G.L., Flichman, D., Mirshahi, F., Sanyal, A.J., and Sookoian, S. (2014). Circulating microRNA signature in non-alcoholic fatty liver disease: From serum non-coding RNAs to liver histology and disease pathogenesis. Gut.","DOI":"10.1136\/gutjnl-2014-306996"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cca.2013.05.021","article-title":"Associations between circulating microRNAs (miR-21, miR-34a, miR-122 and miR-451) and non-alcoholic fatty liver","volume":"424","author":"Yamada","year":"2013","journal-title":"Clin. Chim. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e105192","DOI":"10.1371\/journal.pone.0105192","article-title":"A pilot study of serum MicroRNAs panel as potential biomarkers for diagnosis of nonalcoholic fatty liver disease","volume":"9","author":"Tan","year":"2014","journal-title":"PLoS One"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12169","DOI":"10.1073\/pnas.1412608111","article-title":"Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis","volume":"111","author":"Ward","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1096\/fj.11-187781","article-title":"A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication","volume":"25","author":"Chen","year":"2011","journal-title":"FASEB J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e31952","DOI":"10.1371\/journal.pone.0031952","article-title":"Circulating hepatitis B surface antigen particles carry hepatocellular microRNAs","volume":"7","author":"Novellino","year":"2012","journal-title":"PLoS One"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/jmv.21398","article-title":"Analysis of gene transcription in sera during chronic hepatitis C infection","volume":"81","author":"Carpentier","year":"2009","journal-title":"J. Med. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12884","DOI":"10.1073\/pnas.0704894104","article-title":"Cellular cofactors affecting hepatitis C virus infection and replication","volume":"104","author":"Randall","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1128\/JVI.00417-10","article-title":"Regulation of hepatitis C virus translation and infectious virus production by the MicroRNA miR-122","volume":"84","author":"Jangra","year":"2010","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA","volume":"309","author":"Jopling","year":"2005","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Roberts, A.P.E., Lewis, A.P., and Jopling, C.L. (2011). miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res.","DOI":"10.1093\/nar\/gkr426"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nm.1902","article-title":"Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy","volume":"15","author":"Krol","year":"2009","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e75184","DOI":"10.1371\/journal.pone.0075184","article-title":"Differential stability of cell-free circulating microRNAs: Implications for their utilization as biomarkers","volume":"8","author":"Pleli","year":"2013","journal-title":"PLoS One"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Callegari, E., Gramantieri, L., Domenicali, M., D\u2019Abundo, L., Sabbioni, S., and Negrini, M. (2014). MicroRNAs in liver cancer: A model for investigating pathogenesis and novel therapeutic approaches. Cell Death Differ.","DOI":"10.1038\/cdd.2014.136"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1053\/j.gastro.2007.05.022","article-title":"MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer","volume":"133","author":"Meng","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1053\/j.gastro.2008.04.003","article-title":"MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1","volume":"135","author":"Wong","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/hep.22806","article-title":"MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma","volume":"49","author":"Tsai","year":"2009","journal-title":"Hepatology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3390\/ijms14011105","article-title":"Identification of recurrence related microRNAs in hepatocellular carcinoma after surgical resection","volume":"14","author":"Yang","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.3390\/ijms13078762","article-title":"MicroRNA-125b functions as a tumor suppressor in hepatocellular carcinoma cells","volume":"13","author":"Jia","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/hep.510250418","article-title":"Lack of specificity of albumin-mRNA\u2013positive cells as a marker of circulating hepatoma cells","volume":"25","author":"Muller","year":"1997","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-pathol-121808-102132","article-title":"Nonalcoholic fatty liver disease: Pathology and pathogenesis","volume":"5","author":"Tiniakos","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1002\/hep.22569","article-title":"Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression","volume":"48","author":"Cheung","year":"2008","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/hep.26634","article-title":"Hepatitis C virus induced up-regulation of microRNA-27: A novel mechanism for hepatic steatosis","volume":"59","author":"Singaravelu","year":"2014","journal-title":"Hepatology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.clinbiochem.2013.09.001","article-title":"Measurements of serial plasma levels of albumin mRNA for management of patients post transplant: Does it add value?","volume":"46","author":"Selzner","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e45652","DOI":"10.1371\/journal.pone.0045652","article-title":"Serum MicroRNA-122 predicts survival in patients with liver cirrhosis","volume":"7","author":"Waidmann","year":"2012","journal-title":"PLoS One"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1016\/j.ejca.2013.06.002","article-title":"Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma","volume":"49","author":"Kronenberger","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e24145","DOI":"10.1371\/journal.pone.0024145","article-title":"Haemolysis during sample preparation alters microRNA content of plasma","volume":"6","author":"Kirschner","year":"2011","journal-title":"PLoS One"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1373\/clinchem.2010.157198","article-title":"Analysis of circulating microRNA: Preanalytical and analytical challenges","volume":"57","author":"McDonald","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1158\/1940-6207.CAPR-11-0370","article-title":"Blood cell origin of circulating microRNAs: A cautionary note for cancer biomarker studies","volume":"5","author":"Pritchard","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ymeth.2012.09.015","article-title":"Assessing sample and miRNA profile quality in serum and plasma or other biofluids","volume":"59","author":"Blondal","year":"2013","journal-title":"Methods"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e41561","DOI":"10.1371\/journal.pone.0041561","article-title":"Comparing the MicroRNA Spectrum between Serum and Plasma","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jmoldx.2011.09.002","article-title":"Plasma components affect accuracy of circulating cancer-related microRNA quantitation","volume":"14","author":"Kim","year":"2012","journal-title":"J. Mol. Diagn. JMD"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.clinbiochem.2007.08.006","article-title":"The effect of centrifugation on circulating mRNA quantitation opens up a new scenario in expression profiling from patients with metastatic colorectal cancer","volume":"40","author":"Wong","year":"2007","journal-title":"Clin. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Schageman, J., Zeringer, E., Li, M., Barta, T., Lea, K., Gu, J., Magdaleno, S., Setterquist, R., and Vlassov, A.V. (2013). The complete exosome workflow solution: From isolation to characterization of RNA cargo. BioMed. Res. Int., 2013.","DOI":"10.1155\/2013\/253957"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1196\/annals.1448.006","article-title":"Stability of \u03b2-Actin mRNA in Plasma","volume":"1137","author":"Holford","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e77963","DOI":"10.1371\/journal.pone.0077963","article-title":"Influence of plasma processing on recovery and analysis of circulating nucleic acids","volume":"8","author":"Page","year":"2013","journal-title":"PLoS One"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.jmoldx.2013.07.005","article-title":"Quantification of circulating miRNAs in plasma: Effect of preanalytical and analytical parameters on their isolation and stability","volume":"15","author":"Sourvinou","year":"2013","journal-title":"J. Mol. Diagn."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/cr.2008.282","article-title":"Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases","volume":"18","author":"Chen","year":"2008","journal-title":"Cell Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Jensen, S.G., Lamy, P., Rasmussen, M.H., Ostenfeld, M.S., Dyrskj\u00f8t, L., Orntoft, T.F., and Andersen, C.L. (2011). Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs. BMC Genomics, 12.","DOI":"10.1186\/1471-2164-12-435"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12033-011-9414-6","article-title":"Identification of suitable reference genes for qRT-PCR analysis of circulating microRNAs in hepatitis B virus-infected patients","volume":"50","author":"Zhu","year":"2011","journal-title":"Mol. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrc3066","article-title":"Cell-Free nucleic acids as biomarkers in cancer patients","volume":"11","author":"Schwarzenbach","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e20769","DOI":"10.1371\/journal.pone.0020769","article-title":"Impact of cellular miRNAs on circulating miRNA biomarker signatures","volume":"6","author":"Duttagupta","year":"2011","journal-title":"PLoS One"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kirschner, M.B., van Zandwijk, N., and Reid, G. (2013). Cell-Free microRNAs: Potential biomarkers in need of standardized reporting. Front. Genet., 4.","DOI":"10.3389\/fgene.2013.00056"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/nmeth.2697","article-title":"The need for transparency and good practices in the qPCR literature","volume":"10","author":"Bustin","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/10\/17644\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:16:33Z","timestamp":1760217393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/15\/10\/17644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,30]]},"references-count":97,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10]]}},"alternative-id":["ijms151017644"],"URL":"https:\/\/doi.org\/10.3390\/ijms151017644","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,30]]}}}