{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:43Z","timestamp":1793060023598,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007570","name":"Claussen-Simon-Stiftung","doi-asserted-by":"publisher","award":["Dissertation Plus"],"award-info":[{"award-number":["Dissertation Plus"]}],"id":[{"id":"10.13039\/100007570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003107","name":"Bundesministerium f\u00fcr Gesundheit","doi-asserted-by":"publisher","award":["BMG: 321-4471-02\/157"],"award-info":[{"award-number":["BMG: 321-4471-02\/157"]}],"id":[{"id":"10.13039\/501100003107","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis E virus (HEV) genotypes 3 and 4 (HEV-3, HEV-4) infections are an emerging public health issue in industrialized countries. HEV-3 and \u22124 are usually self-limiting but can progress to chronic hepatitis E in immunocompromised individuals. The molecular mechanisms involved in persistent infections are poorly understood. Micro RNAs (miRNAs) can regulate viral pathogenesis and can serve as novel disease biomarkers. We aimed to explore the modulation of serum miRNAs in patients with acute (AHE) and chronic (CHE) hepatitis E. Both AHE- and CHE-patients exhibited high viral loads (median 3.23E\u2009+\u200905 IU\/mL and 2.11E\u2009+\u200906 IU\/mL, respectively) with HEV-3c being the predominant HEV-genotype. Expression analysis of liver-specific serum miRNAs was performed using real-time PCR. miR-99a-5p, miR-122-5p, and miR-125b-5p were upregulated in AHE (4.70\u20135.28 fold) and CHE patients (2.28\u20136.34 fold), compared to HEV-negative controls. Notably, miR-192-5p was increased 2.57\u00a0fold while miR-125b-5p was decreased 0.35 fold in CHE but not in AHE patients. Furthermore, decreased miR-122-5p expression significantly correlates with reduced liver transaminases in CHE patients. To our knowledge, this marks the first investigation concerning the regulation of circulating liver-specific miRNAs in acute and chronic HEV infections. We found that miR-125b-5p, miR-192-5p, and miR-99a-5p may prove useful in the diagnosis of chronic hepatitis E.<\/jats:p>","DOI":"10.1038\/s41598-020-62159-9","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T11:06:27Z","timestamp":1585047987000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Specific circulating microRNAs during hepatitis E infection can serve as indicator for chronic hepatitis E"],"prefix":"10.1038","volume":"10","author":[{"given":"Dominik","family":"Harms","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Allers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Pietsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.-Patrick","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Hanisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-0052","authenticated-orcid":false,"given":"Jens","family":"Kurreck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2773-486X","authenticated-orcid":false,"given":"C.-Thomas","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"62159_CR1","unstructured":"WHO. Hepatitis E, http:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-e (2019)."},{"key":"62159_CR2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/v8090253","volume":"8","author":"MS Khuroo","year":"2016","unstructured":"Khuroo, M. S., Khuroo, M. S. & Khuroo, N. S. Transmission of Hepatitis E Virus in Developing Countries. Viruses 8, 253, https:\/\/doi.org\/10.3390\/v8090253 (2016).","journal-title":"Viruses"},{"key":"62159_CR3","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/S1473-3099(08)70255-X","volume":"8","author":"HR Dalton","year":"2008","unstructured":"Dalton, H. R., Bendall, R., Ijaz, S. & Banks, M. Hepatitis E: an emerging infection in developed countries. Lancet Infect. Dis. 8, 698\u2013709, https:\/\/doi.org\/10.1016\/S1473-3099(08)70255-X (2008).","journal-title":"Lancet Infect. Dis."},{"key":"62159_CR4","unstructured":"European Centre for Disease Prevention and Control. Hepatitis E in the EU\/EEA, 2005\u20132015. (ECDC, Stockholm, 2017)."},{"key":"62159_CR5","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.jhep.2006.09.016","volume":"46","author":"S Kumar Acharya","year":"2007","unstructured":"Kumar Acharya, S. et al. Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J. Hepatol. 46, 387\u2013394, https:\/\/doi.org\/10.1016\/j.jhep.2006.09.016 (2007).","journal-title":"J. Hepatol."},{"key":"62159_CR6","unstructured":"Sultana, R. & Humayun, S. Fetomaternal outcome in acute hepatitis e. J. Coll. Physicians Surg. Pak. 24, 127\u2013130, 02.2014\/JCPSP.127130 (2014)."},{"key":"62159_CR7","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.jhep.2011.06.021","volume":"56","author":"B Schlosser","year":"2012","unstructured":"Schlosser, B. et al. Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J. Hepatol. 56, 500\u2013502, https:\/\/doi.org\/10.1016\/j.jhep.2011.06.021 (2012).","journal-title":"J. Hepatol."},{"key":"62159_CR8","doi-asserted-by":"publisher","first-page":"e341","DOI":"10.1097\/txd.0000000000000758","volume":"4","author":"M Choi","year":"2018","unstructured":"Choi, M. et al. Prevalence and Clinical Correlates of Chronic Hepatitis E Infection in German Renal Transplant Recipients With Elevated Liver Enzymes. Transplant Direct 4, e341, https:\/\/doi.org\/10.1097\/txd.0000000000000758 (2018).","journal-title":"Transplant Direct"},{"key":"62159_CR9","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1111\/bjh.15672","volume":"184","author":"FF Tang","year":"2019","unstructured":"Tang, F. F. et al. Hepatitis E virus infection after haploidentical haematopoietic stem cell transplantation: incidence and clinical course. Br. J. Haematol. 184, 788\u2013796, https:\/\/doi.org\/10.1111\/bjh.15672 (2019).","journal-title":"Br. J. Haematol."},{"key":"62159_CR10","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1111\/ajt.12253","volume":"13","author":"N Kamar","year":"2013","unstructured":"Kamar, N., Rostaing, L., Legrand-Abravanel, F. & Izopet, J. How should hepatitis E virus infection be defined in organ-transplant recipients? Am. J. Transplant. 13, 1935\u20131936, https:\/\/doi.org\/10.1111\/ajt.12253 (2013).","journal-title":"Am. J. Transplant."},{"issue":"7","key":"62159_CR11","doi-asserted-by":"publisher","first-page":"a031872","DOI":"10.1101\/cshperspect.a031872","volume":"9","author":"Nassim Kamar","year":"2018","unstructured":"Kamar, N. & Pischke, S. Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb. Perspect. Med. 9, https:\/\/doi.org\/10.1101\/cshperspect.a031872 (2019).","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"62159_CR12","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1056\/NEJMoa1215246","volume":"370","author":"N Kamar","year":"2014","unstructured":"Kamar, N. et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N. Engl. J. Med. 370, 1111\u20131120, https:\/\/doi.org\/10.1056\/NEJMoa1215246 (2014).","journal-title":"N. Engl. J. Med."},{"key":"62159_CR13","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1136\/gutjnl-2015-311000","volume":"65","author":"D Todt","year":"2016","unstructured":"Todt, D. et al. In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome. Gut 65, 1733\u20131743, https:\/\/doi.org\/10.1136\/gutjnl-2015-311000 (2016).","journal-title":"Gut"},{"key":"62159_CR14","doi-asserted-by":"publisher","first-page":"283","DOI":"10.3390\/v8100283","volume":"8","author":"D Todt","year":"2016","unstructured":"Todt, D., Walter, S., Brown, R. J. & Steinmann, E. Mutagenic Effects of Ribavirin on Hepatitis E Virus-Viral Extinction versus Selection of Fitness-Enhancing Mutations. Viruses 8, 283, https:\/\/doi.org\/10.3390\/v8100283 (2016).","journal-title":"Viruses"},{"key":"62159_CR15","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nature02871","volume":"431","author":"V Ambros","year":"2004","unstructured":"Ambros, V. The functions of animal microRNAs. Nature 431, 350\u2013355, https:\/\/doi.org\/10.1038\/nature02871 (2004).","journal-title":"Nature"},{"key":"62159_CR16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell. 136, 215\u2013233, https:\/\/doi.org\/10.1016\/j.cell.2009.01.002 (2009).","journal-title":"Cell."},{"key":"62159_CR17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1101\/gr.082701.108","volume":"19","author":"RC Friedman","year":"2009","unstructured":"Friedman, R. C., Farh, K. K., Burge, C. B. & Bartel, D. P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19, 92\u2013105, https:\/\/doi.org\/10.1101\/gr.082701.108 (2009).","journal-title":"Genome Res."},{"key":"62159_CR18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-62703-748-8_2","volume":"1107","author":"KU Tufekci","year":"2014","unstructured":"Tufekci, K. U., Meuwissen, R. L. & Genc, S. The role of microRNAs in biological processes. Methods Mol. Biol. 1107, 15\u201331, https:\/\/doi.org\/10.1007\/978-1-62703-748-8_2 (2014).","journal-title":"Methods Mol. Biol."},{"key":"62159_CR19","first-page":"161","volume":"2","author":"AM Ardekani","year":"2010","unstructured":"Ardekani, A. M. & Naeini, M. M. The Role of MicroRNAs in Human Diseases. Avicenna J. Med. Biotechnol 2, 161\u2013179 (2010).","journal-title":"Avicenna J. Med. Biotechnol"},{"key":"62159_CR20","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1111\/j.1365-2141.2008.07077.x","volume":"141","author":"CH Lawrie","year":"2008","unstructured":"Lawrie, C. H. et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 141, 672\u2013675, https:\/\/doi.org\/10.1111\/j.1365-2141.2008.07077.x (2008).","journal-title":"Br. J. Haematol."},{"key":"62159_CR21","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1373\/clinchem.2010.147850","volume":"56","author":"Y Zhang","year":"2010","unstructured":"Zhang, Y. et al. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin. Chem. 56, 1830\u20131838, https:\/\/doi.org\/10.1373\/clinchem.2010.147850 (2010).","journal-title":"Clin. Chem."},{"key":"62159_CR22","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/j.jhep.2011.11.026","volume":"56","author":"F Borel","year":"2012","unstructured":"Borel, F., Konstantinova, P. & Jansen, P. L. Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J. Hepatol. 56, 1371\u20131383, https:\/\/doi.org\/10.1016\/j.jhep.2011.11.026 (2012).","journal-title":"J. Hepatol."},{"key":"62159_CR23","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/sj.bjc.6606010","volume":"104","author":"S Huang","year":"2011","unstructured":"Huang, S. & He, X. The role of microRNAs in liver cancer progression. Br. J. Cancer 104, 235\u2013240, https:\/\/doi.org\/10.1038\/sj.bjc.6606010 (2011).","journal-title":"Br. J. Cancer"},{"key":"62159_CR24","doi-asserted-by":"publisher","first-page":"9798","DOI":"10.1158\/0008-5472.can-10-1001","volume":"70","author":"LM Li","year":"2010","unstructured":"Li, L. M. et al. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res. 70, 9798\u20139807, https:\/\/doi.org\/10.1158\/0008-5472.can-10-1001 (2010).","journal-title":"Cancer Res."},{"key":"62159_CR25","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/jmv.23540","volume":"85","author":"K Arataki","year":"2013","unstructured":"Arataki, K. et al. 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\u2013798, https:\/\/doi.org\/10.1002\/jmv.23540 (2013).","journal-title":"J. Med. Virol."},{"key":"62159_CR26","doi-asserted-by":"publisher","first-page":"4513","DOI":"10.1007\/s11033-014-3322-3","volume":"41","author":"BG Giray","year":"2014","unstructured":"Giray, B. G. et al. Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma. Mol. Biol. Rep. 41, 4513\u20134519, https:\/\/doi.org\/10.1007\/s11033-014-3322-3 (2014).","journal-title":"Mol. Biol. Rep."},{"key":"62159_CR27","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.jinf.2014.10.017","volume":"70","author":"S Akamatsu","year":"2015","unstructured":"Akamatsu, S. et al. Differences in serum microRNA profiles in hepatitis B and C virus infection. J. Infect. 70, 273\u2013287, https:\/\/doi.org\/10.1016\/j.jinf.2014.10.017 (2015).","journal-title":"J. Infect."},{"key":"62159_CR28","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1093\/infdis\/jix140","volume":"215","author":"MH van der Ree","year":"2017","unstructured":"van der Ree, M. H. et al. Plasma MicroRNA Levels Are Associated With Hepatitis B e Antigen Status and Treatment Response in Chronic Hepatitis B Patients. J. Infect. Dis. 215, 1421\u20131429, https:\/\/doi.org\/10.1093\/infdis\/jix140 (2017).","journal-title":"J. Infect. Dis."},{"key":"62159_CR29","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.jhep.2012.10.015","volume":"58","author":"J Trebicka","year":"2013","unstructured":"Trebicka, J. et al. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis. J. Hepatol. 58, 234\u2013239, https:\/\/doi.org\/10.1016\/j.jhep.2012.10.015 (2013).","journal-title":"J. Hepatol."},{"key":"62159_CR30","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1002\/hep.28660","volume":"64","author":"K Matsuura","year":"2016","unstructured":"Matsuura, K. et al. Circulating let-7 levels in plasma and extracellular vesicles correlate with hepatic fibrosis progression in chronic hepatitis C. Hepatology 64, 732\u2013745, https:\/\/doi.org\/10.1002\/hep.28660 (2016).","journal-title":"Hepatology"},{"key":"62159_CR31","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s11262-013-0912-4","volume":"47","author":"Y Cheng","year":"2013","unstructured":"Cheng, Y. et al. Identification of miR-221 and -222 as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells. Virus Genes 47, 49\u201355, https:\/\/doi.org\/10.1007\/s11262-013-0912-4 (2013).","journal-title":"Virus Genes"},{"key":"62159_CR32","doi-asserted-by":"publisher","first-page":"e01999","DOI":"10.1128\/JVI.01999-17","volume":"92","author":"B Haldipur","year":"2018","unstructured":"Haldipur, B., Bhukya, P. L., Arankalle, V. & Lole, K. Positive Regulation of Hepatitis E Virus Replication by MicroRNA-122. J. Virol. 92, e01999\u201317, https:\/\/doi.org\/10.1128\/JVI.01999-17 (2018).","journal-title":"J. Virol."},{"key":"62159_CR33","doi-asserted-by":"publisher","first-page":"e00287","DOI":"10.1016\/j.heliyon.2017.e00287","volume":"3","author":"N Trehanpati","year":"2017","unstructured":"Trehanpati, N. et al. miRNA signatures can predict acute liver failure in hepatitis E infected pregnant females. Heliyon 3, e00287, https:\/\/doi.org\/10.1016\/j.heliyon.2017.e00287 (2017).","journal-title":"Heliyon"},{"key":"62159_CR34","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1002\/jmv.25471","volume":"91","author":"V Baruah","year":"2019","unstructured":"Baruah, V. & Bose, S. Computational identification of hepatitis E virus-encoded microRNAs and their targets in human. J. Med. Virol. 91, 1545\u20131552, https:\/\/doi.org\/10.1002\/jmv.25471 (2019).","journal-title":"J. Med. Virol."},{"key":"62159_CR35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jviromet.2005.07.004","volume":"131","author":"N Jothikumar","year":"2006","unstructured":"Jothikumar, N., Cromeans, T. L., Robertson, B. H., Meng, X. J. & Hill, V. R. A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J. Virol. Methods 131, 65\u201371, https:\/\/doi.org\/10.1016\/j.jviromet.2005.07.004 (2006).","journal-title":"J. Virol. Methods"},{"key":"62159_CR36","doi-asserted-by":"publisher","unstructured":"Wang, B. et al. Comprehensive Molecular Approach for Characterization of Hepatitis E Virus Genotype 3 Variants. J. Clin. Microbiol. 56, https:\/\/doi.org\/10.1128\/JCM.01686-17 (2018).","DOI":"10.1128\/JCM.01686-17"},{"key":"62159_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, RESEARCH0034, https:\/\/doi.org\/10.1186\/gb-2002-3-7-research0034 (2002).","journal-title":"Genome Biol."},{"key":"62159_CR38","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1099\/jgv.0.000264","volume":"96","author":"DB Smith","year":"2015","unstructured":"Smith, D. B. et al. Variability and pathogenicity of hepatitis E virus genotype 3 variants. J. Gen. Virol. 96, 3255\u20133264, https:\/\/doi.org\/10.1099\/jgv.0.000264 (2015).","journal-title":"J. Gen. Virol."},{"key":"62159_CR39","doi-asserted-by":"publisher","first-page":"10513","DOI":"10.1073\/pnas.0804549105","volume":"105","author":"PS Mitchell","year":"2008","unstructured":"Mitchell, P. S. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 105, 10513\u201310518, https:\/\/doi.org\/10.1073\/pnas.0804549105 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"62159_CR40","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jmoldx.2013.07.005","volume":"15","author":"IS Sourvinou","year":"2013","unstructured":"Sourvinou, I. S., Markou, A. & Lianidou, E. S. Quantification of circulating miRNAs in plasma: effect of preanalytical and analytical parameters on their isolation and stability. J. Mol. Diagn. 15, 827\u2013834, https:\/\/doi.org\/10.1016\/j.jmoldx.2013.07.005 (2013).","journal-title":"J. Mol. Diagn."},{"key":"62159_CR41","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/wrna.1120","volume":"3","author":"P Chugh","year":"2012","unstructured":"Chugh, P. & Dittmer, D. P. Potential pitfalls in microRNA profiling. Wiley Interdiscip Rev RNA 3, 601\u2013616, https:\/\/doi.org\/10.1002\/wrna.1120 (2012).","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"62159_CR42","doi-asserted-by":"publisher","first-page":"4683","DOI":"10.3892\/mmr.2015.3919","volume":"12","author":"Y Li","year":"2015","unstructured":"Li, Y. et al. Assessment of endogenous reference gene suitability for serum exosomal microRNA expression analysis in liver carcinoma resection studies. Mol. Med. Rep. 12, 4683\u20134691, https:\/\/doi.org\/10.3892\/mmr.2015.3919 (2015).","journal-title":"Mol. Med. Rep."},{"key":"62159_CR43","doi-asserted-by":"publisher","first-page":"137","DOI":"10.4161\/rna.18827","volume":"9","author":"C Jopling","year":"2012","unstructured":"Jopling, C. Liver-specific microRNA-122: Biogenesis and function. RNA Biol. 9, 137\u2013142, https:\/\/doi.org\/10.4161\/rna.18827 (2012).","journal-title":"RNA Biol."},{"key":"62159_CR44","doi-asserted-by":"publisher","first-page":"e0142661","DOI":"10.1371\/journal.pone.0142661","volume":"10","author":"PP Becker","year":"2015","unstructured":"Becker, P. P. et al. Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis. PLoS One 10, e0142661, https:\/\/doi.org\/10.1371\/journal.pone.0142661 (2015).","journal-title":"PLoS One"},{"key":"62159_CR45","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1007\/s13238-012-2036-3","volume":"3","author":"J Hu","year":"2012","unstructured":"Hu, J. et al. MiR-122 in hepatic function and liver diseases. Protein Cell. 3, 364\u2013371, https:\/\/doi.org\/10.1007\/s13238-012-2036-3 (2012).","journal-title":"Protein Cell."},{"key":"62159_CR46","doi-asserted-by":"publisher","first-page":"10574","DOI":"10.1074\/jbc.M117.785592","volume":"292","author":"A Morimoto","year":"2017","unstructured":"Morimoto, A. et al. An HNF4alpha-microRNA-194\/192 signaling axis maintains hepatic cell function. J. Biol. Chem. 292, 10574\u201310585, https:\/\/doi.org\/10.1074\/jbc.M117.785592 (2017).","journal-title":"J. Biol. Chem."},{"key":"62159_CR47","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2147\/ott.s114276","volume":"11","author":"TF Tsai","year":"2018","unstructured":"Tsai, T. F. et al. miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells. Onco Targets Ther. 11, 239\u2013252, https:\/\/doi.org\/10.2147\/ott.s114276 (2018).","journal-title":"Onco Targets Ther."},{"key":"62159_CR48","first-page":"1755","volume":"20","author":"M Xia","year":"2016","unstructured":"Xia, M., Li, H., Wang, J. J., Zeng, H. J. & Wang, S. H. MiR-99a suppress proliferation, migration and invasion through regulating insulin-like growth factor 1 receptor in breast cancer. Eur. Rev. Med. Pharmacol. Sci. 20, 1755\u20131763 (2016).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"62159_CR49","doi-asserted-by":"publisher","first-page":"e0185636","DOI":"10.1371\/journal.pone.0185636","volume":"12","author":"LL Mei","year":"2017","unstructured":"Mei, L. L. et al. miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma. PLoS One 12, e0185636, https:\/\/doi.org\/10.1371\/journal.pone.0185636 (2017).","journal-title":"PLoS One"},{"key":"62159_CR50","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1002\/ijc.25575","volume":"128","author":"Y Guan","year":"2011","unstructured":"Guan, Y., Yao, H., Zheng, Z., Qiu, G. & Sun, K. MiR-125b targets BCL3 and suppresses ovarian cancer proliferation. Int. J. Cancer 128, 2274\u20132283, https:\/\/doi.org\/10.1002\/ijc.25575 (2011).","journal-title":"Int. J. Cancer"},{"key":"62159_CR51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.chom.2008.05.013","volume":"4","author":"CL Jopling","year":"2008","unstructured":"Jopling, C. L., Schutz, S. & Sarnow, P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell. Host Microbe 4, 77\u201385, https:\/\/doi.org\/10.1016\/j.chom.2008.05.013 (2008).","journal-title":"Cell. Host Microbe"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62159-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62159-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62159-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T08:48:54Z","timestamp":1670316534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62159-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["62159"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-62159-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]},"assertion":[{"value":"17 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5337"}}