{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:34:27Z","timestamp":1791819267604,"version":"4.3.4"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T00:00:00Z","timestamp":1613260800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670851"],"award-info":[{"award-number":["31670851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) is a malignant disease with high morbidity and mortality, and the molecular mechanism for the genesis and progression is complex and heterogeneous. Biomarker discovery is crucial for the personalized and precision treatment of HCC. The accumulation of reported microRNA biomarkers makes it possible to combine computational identification with experimental validation to accelerate the discovery of novel biomarker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the present work, we applied a rational computer\u2010aided biomarker discovery model to screen for the HCC diagnosis biomarker. Two HCC\u2010associated networks were constructed based on the microRNA and mRNA expression profiles, and the potential microRNA biomarkers were identified based on their unique regulatory and influential power in the network. These putative biomarkers were then experimentally validated. One prominent example among these identified biomarkers is MiR\u2010378a\u20103p: It was shown to independently regulate several important transcription factors such as PLAGL2 and \u03b2\u2010catenin, affecting the \u03b2\u2010catenin signaling. Such mechanism may indicate a potential tumor suppressor role of MiR\u2010378a\u20103p and the impact of its abnormal expression on the cell growth and invasion of HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A bioinformatics model with network topological and functional characterization was successfully applied to the identification of HCC biomarkers. The predicted microRNA biomarkers were than validated with experiments using human HCC cell lines, model animal, and clinical specimens. The results confirmed the prediction by our proposed model that miR\u2010378a\u20103p was a putative biomarker for diagnosis and prognosis of HCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.307","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T17:57:06Z","timestamp":1613325426000},"source":"Crossref","is-referenced-by-count":19,"title":["MiR\u2010378a\u20103p as a putative biomarker for hepatocellular carcinoma diagnosis and prognosis: Computational screening with experimental validation"],"prefix":"10.1002","volume":"11","author":[{"given":"Fuliang","family":"Qian","sequence":"first","affiliation":[{"name":"Center for Systems Biology Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of the First Biliary Surgery, Shanghai\u00a0Eastern Hepatobiliary Surgery Hospital Navy Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of the First Biliary Surgery, Shanghai\u00a0Eastern Hepatobiliary Surgery Hospital Navy Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-575X","authenticated-orcid":false,"given":"Wenying","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Systems Biology Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Institutes for Systems Genetics, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Systems Biology Soochow University  Suzhou China"},{"name":"Department of Oncology The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of the First Biliary Surgery, Shanghai\u00a0Eastern Hepatobiliary Surgery Hospital Navy Military Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-1531","authenticated-orcid":false,"given":"Bairong","family":"Shen","sequence":"additional","affiliation":[{"name":"Institutes for Systems Genetics, Frontiers Science Center for Disease\u2010related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx158"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2011.03.004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300141"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr770"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep45477"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu811"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1109\/TNB.2013.2279131"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-3498-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0055"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2mb25180a"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-66"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-169"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4459"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.05.020"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.01.001"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.04.031"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2607"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02597.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-3070-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1266"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1161"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn851"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn714"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.03.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013534"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1248"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1056"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1536"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2538"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1181"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj112"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-7-S3-S6"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1506-7"},{"issue":"8","key":"e_1_2_10_36_1","first-page":"1093","article-title":"MiRNA\u2010BD: an evidence\u2010based bioinformatics model and software tool for microRNA biomarker discovery","volume":"15","author":"Lin Y","year":"2018","journal-title":"RNA Biol"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-02-074617"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24509"},{"issue":"6","key":"e_1_2_10_40_1","first-page":"1149","article-title":"Impairment of clathrin\u2010mediated endocytosis via cytoskeletal change by epithelial to fibroblastoid conversion in HepG2 cells: a possible mechanism of des\u2010gamma\u2010carboxy prothrombin production in hepatocellular carcinoma","volume":"33","author":"Murata K","year":"2008","journal-title":"Int J Oncol"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205248"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006685218766"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh070"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-013-2745-3"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.03.020"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0883-4"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-9-47"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29544"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.178"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907904107"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0092"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2015.68"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12510"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.01.111"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087606"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.29688"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2015.11.002"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2013.1638"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4980"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2886"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.10.030"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.10.028"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.10.053"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004873"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093707"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-012-2317-y"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3166"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.410506"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4491"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.307","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ctm2.307","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T20:39:37Z","timestamp":1692391177000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":69,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/ctm2.307"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.307","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]},"article-number":"e307"}}