{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T14:00:02Z","timestamp":1783778402036,"version":"3.55.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to investigate pathogenesis and novel diagnostic biomarkers of biliary atresia (BA). Serum samples from infants with BA and non-BA neonatal cholestasis (NC) were collected for miRNA microarray analysis and then differentially expressed miRNAs were screened. Differentially expressed miRNAs were validated by qRT-PCR using an independent serum samples from infants with BA and NC. Diagnostic utility of validated miRNAs was further analyzed using serum samples by receiver-operating characteristic curve analysis. Totally, 13 differentially expressed miRNAs were identified including 11 down-regulated and 2 up-regulated ones. Target genes of hsa-miR-4429 and hsa-miR-4689 were significantly involved in FoxO signaling pathway. Eight differentially expressed miRNAs were chosen for validation by qRT-PCR analysis and four miRNAs (hsa-miR-150-3p, hsa-miR-4429, hsa-miR-4689 and hsa-miR-92a-3p) were differentially expressed. The area under the curve of hsa-miR-4429 and hsa-miR-4689 was 0.789 (sensitivity\u2009=\u200983.33%, specificity\u2009=\u200980.00%) and 0.722 (sensitivity\u2009=\u200966.67%, specificity\u2009=\u200980.00%), respectively. Differentially expressed miRNAs including hsa-miR-4429 and hsa-miR-4689 might play critical roles in BA by regulating their target genes and these two miRNAs may have the potential to become diagnostic biomarkers.<\/jats:p>","DOI":"10.1038\/srep21084","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T10:49:27Z","timestamp":1455619767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Serum microRNA microarray analysis identifies miR-4429 and miR-4689 are potential diagnostic biomarkers for biliary atresia"],"prefix":"10.1038","volume":"6","author":[{"given":"Rui","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"BFsrep21084_CR1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1055\/s-0032-1329899","volume":"32","author":"CL Mack","year":"2012","unstructured":"Mack, C. L., Feldman, A. G. & Sokol, R. J. Clues to the etiology of bile duct injury in biliary atresia. Seminars in liver disease 32, 307\u2013316, doi: 10.1055\/s-0032-1329899 (2012).","journal-title":"Seminars in liver disease"},{"key":"BFsrep21084_CR2","doi-asserted-by":"crossref","unstructured":"Mack, C. L. What Causes Biliary Atresia? Unique Aspects of the Neonatal Immune System Provide Clues to Disease Pathogenesis. CMGH Cellular and Molecular Gastroenterology and Hepatology (2015).","DOI":"10.1016\/j.jcmgh.2015.04.001"},{"key":"BFsrep21084_CR3","doi-asserted-by":"crossref","unstructured":"Zhou, K. et al. Metabonomics Reveals Metabolite Changes in Biliary Atresia Infants. J Proteome Res, doi: 10.1021\/acs.jproteome.5b00125 (2015).","DOI":"10.1021\/acs.jproteome.5b00125"},{"key":"BFsrep21084_CR4","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1097\/MPG.0b013e3181cb42ee","volume":"50","author":"H Wang","year":"2010","unstructured":"Wang, H. et al. Serum markers may distinguish biliary atresia from other forms of neonatal cholestasis. Journal of pediatric gastroenterology and nutrition 50, 411\u2013416, doi: 10.1097\/MPG.0b013e3181cb42ee (2010).","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"key":"BFsrep21084_CR5","first-page":"236","volume":"14","author":"K Felekkis","year":"2010","unstructured":"Felekkis, K., Touvana, E., Stefanou, C. & Deltas, C. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia 14, 236\u2013240 (2010).","journal-title":"Hippokratia"},{"key":"BFsrep21084_CR6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1097\/MPG.0b013e318244148b","volume":"54","author":"NJ Hand","year":"2012","unstructured":"Hand, N. J. et al. MicroRNA profiling identifies miR-29 as a regulator of disease-associated pathways in experimental biliary atresia. Journal of pediatric gastroenterology and nutrition 54, 186\u2013192, doi: 10.1097\/MPG.0b013e318244148b (2012).","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"key":"BFsrep21084_CR7","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1752-0509-7-104","volume":"7","author":"K Bessho","year":"2013","unstructured":"Bessho, K. et al. Integrative genomics identifies candidate microRNAs for pathogenesis of experimental biliary atresia. BMC systems biology 7, 104, doi: 10.1186\/1752-0509-7-104 (2013).","journal-title":"BMC systems biology"},{"key":"BFsrep21084_CR8","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.bbrc.2014.02.065","volume":"446","author":"WJ Shen","year":"2014","unstructured":"Shen, W. J., Dong, R., Chen, G. & Zheng, S. microRNA-222 modulates liver fibrosis in a murine model of biliary atresia. Biochemical and biophysical research communications 446, 155\u2013159, doi: 10.1016\/j.bbrc.2014.02.065 (2014).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep21084_CR9","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.cellsig.2014.01.003","volume":"26","author":"Y Xiao","year":"2014","unstructured":"Xiao, Y. et al. Up-regulation of miR-200b in biliary atresia patients accelerates proliferation and migration of hepatic stallate cells by activating PI3K\/Akt signaling. Cellular signalling 26, 925\u2013932, doi: 10.1016\/j.cellsig.2014.01.003 (2014).","journal-title":"Cellular signalling"},{"key":"BFsrep21084_CR10","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1097\/MOP.0000000000000214","volume":"27","author":"JA Zagory","year":"2015","unstructured":"Zagory, J. A., Nguyen, M. V. & Wang, K. S. Recent advances in the pathogenesis and management of biliary atresia. Current opinion in pediatrics 27, 389\u2013394, doi: 10.1097\/MOP.0000000000000214 (2015).","journal-title":"Current opinion in pediatrics"},{"key":"BFsrep21084_CR11","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/cr.2008.282","volume":"18","author":"X Chen","year":"2008","unstructured":"Chen, X. et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell research 18, 997\u20131006, doi: 10.1038\/cr.2008.282 (2008).","journal-title":"Cell research"},{"key":"BFsrep21084_CR12","doi-asserted-by":"crossref","unstructured":"Zahm, A. M. et al. Circulating MicroRNA Is a Biomarker of Pediatric Crohn Disease. Journal of pediatric gastroenterology and nutrition 53, 10.1097\/MPG.1090b1013e31822200cc, doi: 10.1097\/MPG.0b013e31822200cc (2011).","DOI":"10.1097\/MPG.0b013e31822200cc"},{"key":"BFsrep21084_CR13","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1097\/MPG.0b013e318264e648","volume":"55","author":"AM Zahm","year":"2012","unstructured":"Zahm, A. M., Hand, N. J., Boateng, L. A. & Friedman, J. R. Circulating MicroRNA is a Biomarker of Biliary Atresia. Journal of pediatric gastroenterology and nutrition 55, 366\u2013369, doi: 10.1097\/MPG.0b013e318264e648 (2012).","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"key":"BFsrep21084_CR14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1471-2164-7-59","volume":"7","author":"Y Wang","year":"2006","unstructured":"Wang, Y. et al. Large scale real-time PCR validation on gene expression measurements from two commercial long-oligonucleotide microarrays. BMC genomics 7, 59, doi: 10.1186\/1471-2164-7-59 (2006).","journal-title":"BMC genomics"},{"key":"BFsrep21084_CR15","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/hep.21790","volume":"46","author":"RJ Sokol","year":"2007","unstructured":"Sokol, R. J. et al. Screening and outcomes in biliary atresia: summary of a National Institutes of Health workshop. Hepatology 46, 566\u2013581, doi: 10.1002\/hep.21790 (2007).","journal-title":"Hepatology"},{"key":"BFsrep21084_CR16","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1046\/j.1440-1746.2000.02091.x","volume":"15","author":"M Strazzabosco","year":"2000","unstructured":"Strazzabosco, M., Spirli, C. & Okolicsanyi, L. Pathophysiology of the intrahepatic biliary epithelium. Journal of gastroenterology and hepatology 15, 244\u2013253 (2000).","journal-title":"Journal of gastroenterology and hepatology"},{"key":"BFsrep21084_CR17","doi-asserted-by":"publisher","first-page":"S44","DOI":"10.1016\/j.pan.2015.05.477","volume":"15","author":"MT Guerra","year":"2015","unstructured":"Guerra, M. T. & Nathanson, M. H. Calcium signaling and secretion in cholangiocytes. Pancreatology 15, S44\u201348, doi: 10.1016\/j.pan.2015.05.477 (2015).","journal-title":"Pancreatology"},{"key":"BFsrep21084_CR18","doi-asserted-by":"publisher","first-page":"3466","DOI":"10.3748\/wjg.v12.i22.3466","volume":"12","author":"N Minagawa","year":"2006","unstructured":"Minagawa, N., Ehrlich, B. E. & Nathanson, M. H. Calcium signaling in cholangiocytes. World journal of gastroenterology 12, 3466\u20133470 (2006).","journal-title":"World journal of gastroenterology"},{"key":"BFsrep21084_CR19","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1055\/s-2007-985068","volume":"27","author":"CL Mack","year":"2007","unstructured":"Mack, C. L. The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Seminars in liver disease 27, 233\u2013242, doi: 10.1055\/s-2007-985068 (2007).","journal-title":"Seminars in liver disease"},{"key":"BFsrep21084_CR20","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1111\/liv.12030","volume":"33","author":"J Kopycinska","year":"2013","unstructured":"Kopycinska, J. et al. Activation of FoxO3a\/Bim axis in patients with Primary Biliary Cirrhosis. Liver Int 33, 231\u2013238 (2013).","journal-title":"Liver Int"},{"key":"BFsrep21084_CR21","doi-asserted-by":"publisher","first-page":"e87660","DOI":"10.1371\/journal.pone.0087660","volume":"9","author":"XS Ren","year":"2014","unstructured":"Ren, X. S. et al. Activation of the PI3K\/mTOR Pathway Is Involved in Cystic Proliferation of Cholangiocytes of the PCK Rat. PloS one 9, e87660, doi: 10.1371\/journal.pone.0087660 (2014).","journal-title":"PloS one"},{"key":"BFsrep21084_CR22","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1111\/j.1442-200X.2010.03275.x","volume":"52","author":"A Shalaby","year":"2010","unstructured":"Shalaby, A., Makin, E. & Davenport, M. Classification of the biliary atresia phenotype. Pediatrics international : official journal of the Japan Pediatric Society 52, 897, doi: 10.1111\/j.1442-200X.2010.03275.x (2010).","journal-title":"Pediatrics international : official journal of the Japan Pediatric Society"},{"key":"BFsrep21084_CR23","doi-asserted-by":"publisher","first-page":"e68602","DOI":"10.1371\/journal.pone.0068602","volume":"8","author":"R Dong","year":"2013","unstructured":"Dong, R. et al. Identification of HSP90 as potential biomarker of biliary atresia using two-dimensional electrophoresis and mass spectrometry. PloS one 8, e68602, doi: 10.1371\/journal.pone.0068602 (2013).","journal-title":"PloS one"},{"key":"BFsrep21084_CR24","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1097\/MPG.0b013e3181cb42ee","volume":"50","author":"H Wang","year":"2010","unstructured":"Wang, H. et al. Serum markers may distinguish biliary atresia from other forms of neonatal cholestasis. Journal of pediatric gastroenterology and nutrition 50, 411\u2013416, doi: 10.1097\/MPG.0b013e3181cb42ee (2010).","journal-title":"Journal of pediatric gastroenterology and nutrition"},{"key":"BFsrep21084_CR25","unstructured":"Warnes, G. et al. (2011)."},{"key":"BFsrep21084_CR26","doi-asserted-by":"publisher","first-page":"P3","DOI":"10.1186\/gb-2003-4-5-p3","volume":"4","author":"G Dennis Jr","year":"2003","unstructured":"Dennis Jr, G. et al. DAVID: database for annotation, visualization and integrated discovery. Genome Biol 4, P3 (2003).","journal-title":"Genome Biol"},{"key":"BFsrep21084_CR27","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/978-1-60761-987-1_18","volume":"696","author":"M Kohl","year":"2011","unstructured":"Kohl, M., Wiese, S. & Warscheid, B. Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696, 291\u2013303, doi: 10.1007\/978-1-60761-987-1_18 (2011).","journal-title":"Methods Mol Biol"},{"key":"BFsrep21084_CR28","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1002\/ijc.28757","volume":"135","author":"J Hu","year":"2014","unstructured":"Hu, J. et al. Human miR-1228 as a stable endogenous control for the quantification of circulating microRNAs in cancer patients. International Journal of Cancer 135, 1187\u20131194, doi: 10.1002\/ijc.28757 (2014).","journal-title":"International Journal of Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep21084","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21084.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:07:28Z","timestamp":1672841248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep21084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,16]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,26]]}},"alternative-id":["BFsrep21084"],"URL":"https:\/\/doi.org\/10.1038\/srep21084","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,16]]},"assertion":[{"value":"3 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21084"}}