{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:14:35Z","timestamp":1792800875976,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81372327"],"award-info":[{"award-number":["81372327"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572427"],"award-info":[{"award-number":["81572427"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874189"],"award-info":[{"award-number":["81874189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572855"],"award-info":[{"award-number":["81572855"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874065"],"award-info":[{"award-number":["81874065"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874149"],"award-info":[{"award-number":["81874149"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Hepato-Biliary-Pancreatic Investigation Fund of Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province","award":["CXPJJH11800001-2018356"],"award-info":[{"award-number":["CXPJJH11800001-2018356"]}]},{"name":"the State Key Project on Infection Disease of China","award":["2018ZX10723204-003"],"award-info":[{"award-number":["2018ZX10723204-003"]}]},{"name":"the National Key Research and Development Program of China","award":["2018YFA0208904"],"award-info":[{"award-number":["2018YFA0208904"]}]},{"name":"Major Technological Innovation Projects of Hubei Province","award":["2018ACA137"],"award-info":[{"award-number":["2018ACA137"]}]},{"name":"the HCP project of Huazhong University of Science and Technology","award":["5001540006"],"award-info":[{"award-number":["5001540006"]}],"id":[{"id":"https:\/\/ror.org\/00p991c53","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the HCP project of Huazhong University of Science and Technology","award":["5001540059"],"award-info":[{"award-number":["5001540059"]}],"id":[{"id":"https:\/\/ror.org\/00p991c53","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is one of the most prevalent common cancer worldwide with high mortality. Transforming growth factor-\u03b2 (TGF-\u03b2) signaling pathway was reported dysregulated during liver cancer formation and progression. As a key component of TGF-\u03b2 signaling, the role of SMAD2 and its regulatory mechanisms in HCC remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SMAD2 expression in paired HCC specimens were determined by western blot and immunohistochemistry (IHC). quantitative real-time PCR (qRT-PCR) was used to measure mRNA and microRNA (miRNA) expression level. Cell migration, invasion and proliferation ability were evaluated by transwell, CCK8 and EdU assay. In silico websites were used to manifest overall survival rates of HCC patients or to predict miRNAs targeting SMAD2. Dual luciferase reporter assay and anti-Ago2 immunoprecipitation assay were performed to confirm the binding between SMAD2 mRNA and miRNA-148a-3p (miR-148a). Tumorigenesis and lung metastasis mouse model were used to explore the role of miR-148a in vivo. In situ hybridization (ISH) was conducted to determine the expression of miR-148a in liver tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we found that SMAD2 was highly expressed in HCC and elevated SMAD2 expression predicted shorter overall survival (OS) time for HCC patients. SMAD2 promoted mobility and proliferation of HCC cells in vitro. We further revealed that the expression of miR-148a was negatively correlated with SMAD2 and found that miR-148a repressed SMAD2 expression by downregulating its mRNA through binding with Argonaute 2 (Ago2) in HCC. Transwell, CCK8 and animal experiments exhibited miR-148a inhibited metastasis and proliferation of HCC in vitro and in vivo. Moreover, the phenotype changes caused by miR-148a manipulation were recovered by rescuing SMAD2 expression in HCC cells. ISH assay indicated miR-148a was downregulated in HCC and low expression of miR-148a associated with more aggressive clinic features and poor prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>miR-148a was identified as a repressor of HCC progression by downregulating SMAD2 in an Ago2 dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-020-01649-0","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:46:22Z","timestamp":1596501982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["MicroRNA-148a-3p inhibits progression of hepatocelluar carcimoma by repressing SMAD2 expression in an Ago2 dependent manner"],"prefix":"10.1186","volume":"39","author":[{"given":"Zhao","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"1649_CR1","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1056\/NEJMra1713263","volume":"380","author":"A Villanueva","year":"2019","unstructured":"Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380:1450\u201362.","journal-title":"N Engl J Med"},{"key":"1649_CR2","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","volume":"16","author":"JD Yang","year":"2019","unstructured":"Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589\u2013604.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"1649_CR3","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394\u2013424.","journal-title":"CA Cancer J Clin"},{"key":"1649_CR4","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","volume":"134","author":"J Massague","year":"2008","unstructured":"Massague J. TGFbeta in cancer. Cell. 2008;134:215\u201330.","journal-title":"Cell"},{"key":"1649_CR5","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","volume":"113","author":"Y Shi","year":"2003","unstructured":"Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113:685\u2013700.","journal-title":"Cell"},{"key":"1649_CR6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.molcel.2008.01.006","volume":"29","author":"J Massague","year":"2008","unstructured":"Massague J. A very private TGF-beta receptor embrace. Mol Cell. 2008;29:149\u201350.","journal-title":"Mol Cell"},{"key":"1649_CR7","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.tibs.2015.03.012","volume":"40","author":"MJ Macias","year":"2015","unstructured":"Macias MJ, Martin-Malpartida P, Massague J. Structural determinants of Smad function in TGF-beta signaling. Trends Biochem Sci. 2015;40:296\u2013308.","journal-title":"Trends Biochem Sci"},{"key":"1649_CR8","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1038\/onc.2009.426","volume":"29","author":"M Petersen","year":"2010","unstructured":"Petersen M, Pardali E, van der Horst G, Cheung H, van den Hoogen C, van der Pluijm G, Ten Dijke P. Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis. Oncogene. 2010;29:1351\u201361.","journal-title":"Oncogene"},{"key":"1649_CR9","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/1476-4598-10-67","volume":"10","author":"H Ungefroren","year":"2011","unstructured":"Ungefroren H, Groth S, Sebens S, Lehnert H, Gieseler F, Fandrich F. Differential roles of Smad2 and Smad3 in the regulation of TGF-beta1-mediated growth inhibition and cell migration in pancreatic ductal adenocarcinoma cells: control by Rac1. Mol Cancer. 2011;10:67.","journal-title":"Mol Cancer"},{"key":"1649_CR10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1002\/jcb.21255","volume":"101","author":"KA Brown","year":"2007","unstructured":"Brown KA, Pietenpol JA, Moses HL. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem. 2007;101:9\u201333.","journal-title":"J Cell Biochem"},{"key":"1649_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.immuni.2015.06.010","volume":"43","author":"I Kashiwagi","year":"2015","unstructured":"Kashiwagi I, Morita R, Schichita T, Komai K, Saeki K, Matsumoto M, Takeda K, et al. Smad2 and Smad3 inversely regulate TGF-beta autoinduction in Clostridium butyricum-activated dendritic cells. Immunity. 2015;43:65\u201379.","journal-title":"Immunity"},{"key":"1649_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/S1097-2765(00)80119-7","volume":"2","author":"E Labbe","year":"1998","unstructured":"Labbe E, Silvestri C, Hoodless PA, Wrana JL, Attisano L. Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2. Mol Cell. 1998;2:109\u201320.","journal-title":"Mol Cell"},{"key":"1649_CR13","doi-asserted-by":"publisher","unstructured":"Liao Z, Chen L, Zhang X, Zhang H, Tan X, Dong K, Lu X, et al. PTPRepsilon acts as a metastatic promoter in hepatocellular carcinoma by facilitating recruitment of SMAD3 to TGF-beta receptor 1. Hepatology. 2020. https:\/\/doi.org\/10.1002\/hep.31104.","DOI":"10.1002\/hep.31104"},{"key":"1649_CR14","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1016\/j.jaci.2017.08.034","volume":"141","author":"TX Lu","year":"2018","unstructured":"Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141:1202\u20137.","journal-title":"J Allergy Clin Immunol"},{"key":"1649_CR15","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.tig.2018.12.005","volume":"35","author":"LB Chipman","year":"2019","unstructured":"Chipman LB, Pasquinelli AE. miRNA targeting: growing beyond the seed. Trends Genet. 2019;35:215\u201322.","journal-title":"Trends Genet"},{"key":"1649_CR16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.cell.2012.05.017","volume":"150","author":"E Elkayam","year":"2012","unstructured":"Elkayam E, Kuhn CD, Tocilj A, Haase AD, Greene EM, Hannon GJ, Joshua-Tor L. The structure of human argonaute-2 in complex with miR-20a. Cell. 2012;150:100\u201310.","journal-title":"Cell"},{"key":"1649_CR17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.cell.2018.03.006","volume":"173","author":"DP Bartel","year":"2018","unstructured":"Bartel DP. Metazoan MicroRNAs. Cell. 2018;173:20\u201351.","journal-title":"Cell"},{"key":"1649_CR18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.addr.2014.10.029","volume":"81","author":"N Yang","year":"2015","unstructured":"Yang N, Ekanem NR, Sakyi CA, Ray SD. Hepatocellular carcinoma and microRNA: new perspectives on therapeutics and diagnostics. Adv Drug Deliv Rev. 2015;81:62\u201374.","journal-title":"Adv Drug Deliv Rev"},{"key":"1649_CR19","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/hep.23010","volume":"50","author":"JL Mott","year":"2009","unstructured":"Mott JL. MicroRNAs involved in tumor suppressor and oncogene pathways: implications for hepatobiliary neoplasia. Hepatology. 2009;50:630\u20137.","journal-title":"Hepatology"},{"key":"1649_CR20","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1002\/hep.26095","volume":"57","author":"S Giordano","year":"2013","unstructured":"Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013;57:840\u20137.","journal-title":"Hepatology"},{"key":"1649_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s40001-014-0068-2","volume":"19","author":"L Pan","year":"2014","unstructured":"Pan L, Huang S, He R, Rong M, Dang Y, Chen G. Decreased expression and clinical significance of miR-148a in hepatocellular carcinoma tissues. Eur J Med Res. 2014;19:68.","journal-title":"Eur J Med Res"},{"key":"1649_CR22","first-page":"630","volume":"123","author":"X Xu","year":"2013","unstructured":"Xu X, Fan Z, Kang L, Han J, Jiang C, Zheng X, Zhu Z, et al. Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis. J Clin Invest. 2013;123:630\u201345.","journal-title":"J Clin Invest"},{"key":"1649_CR23","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1002\/hep.26422","volume":"58","author":"L Gailhouste","year":"2013","unstructured":"Gailhouste L, Gomez-Santos L, Hagiwara K, Hatada I, Kitagawa N, Kawaharada K, Thirion M, et al. miR-148a plays a pivotal role in the liver by promoting the hepatospecific phenotype and suppressing the invasiveness of transformed cells. Hepatology. 2013;58:1153\u201365.","journal-title":"Hepatology"},{"key":"1649_CR24","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1002\/hep.27273","volume":"60","author":"ZY Ding","year":"2014","unstructured":"Ding ZY, Jin GN, Wang W, Chen WX, Wu YH, Ai X, Chen L, et al. Reduced expression of transcriptional intermediary factor 1 gamma promotes metastasis and indicates poor prognosis of hepatocellular carcinoma. Hepatology. 2014;60:1620\u201336.","journal-title":"Hepatology"},{"key":"1649_CR25","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Tang","year":"2017","unstructured":"Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98\u2013W102.","journal-title":"Nucleic Acids Res"},{"key":"1649_CR26","doi-asserted-by":"publisher","first-page":"181006","DOI":"10.1098\/rsos.181006","volume":"5","author":"O Menyhart","year":"2018","unstructured":"Menyhart O, Nagy A, Gyorffy B. Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci. 2018;5:181006.","journal-title":"R Soc Open Sci"},{"key":"1649_CR27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15\u201320.","journal-title":"Cell"},{"key":"1649_CR28","doi-asserted-by":"publisher","first-page":"D296","DOI":"10.1093\/nar\/gkx1067","volume":"46","author":"CH Chou","year":"2018","unstructured":"Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, Huang WC, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46:D296\u2013302.","journal-title":"Nucleic Acids Res"},{"key":"1649_CR29","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1093\/bioinformatics\/bts344","volume":"28","author":"A Jeggari","year":"2012","unstructured":"Jeggari A, Marks DS, Larsson E. miRcode: a map of putative microRNA target sites in the long non-coding transcriptome. Bioinformatics. 2012;28:2062\u20133.","journal-title":"Bioinformatics"},{"key":"1649_CR30","doi-asserted-by":"publisher","first-page":"D92","DOI":"10.1093\/nar\/gkt1248","volume":"42","author":"JH Li","year":"2014","unstructured":"Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42:D92\u20137.","journal-title":"Nucleic Acids Res"},{"key":"1649_CR31","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1172\/JCI90439","volume":"127","author":"Z Ying","year":"2017","unstructured":"Ying Z, Tian H, Li Y, Lian R, Li W, Wu S, Zhang HZ, et al. CCT6A suppresses SMAD2 and promotes prometastatic TGF-beta signaling. J Clin Invest. 2017;127:1725\u201340.","journal-title":"J Clin Invest"},{"key":"1649_CR32","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1615\/CritRevEukarGeneExpr.v17.i4.30","volume":"17","author":"C Millet","year":"2007","unstructured":"Millet C, Zhang YE. Roles of Smad3 in TGF-beta signaling during carcinogenesis. Crit Rev Eukaryot Gene Expr. 2007;17:281\u201393.","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"1649_CR33","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.tips.2012.04.003","volume":"33","author":"H Butz","year":"2012","unstructured":"Butz H, Racz K, Hunyady L, Patocs A. Crosstalk between TGF-beta signaling and the microRNA machinery. Trends Pharmacol Sci. 2012;33:382\u201393.","journal-title":"Trends Pharmacol Sci"},{"key":"1649_CR34","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1002\/hep.28367","volume":"63","author":"KH Jung","year":"2016","unstructured":"Jung KH, Zhang J, Zhou C, Shen H, Gagea M, Rodriguez-Aguayo C, Lopez-Berestein G, et al. Differentiation therapy for hepatocellular carcinoma: multifaceted effects of miR-148a on tumor growth and phenotype and liver fibrosis. Hepatology. 2016;63:864\u201379.","journal-title":"Hepatology"},{"key":"1649_CR35","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1002\/mc.22064","volume":"53","author":"H Yan","year":"2014","unstructured":"Yan H, Dong X, Zhong X, Ye J, Zhou Y, Yang X, Shen J, et al. Inhibitions of epithelial to mesenchymal transition and cancer stem cells-like properties are involved in miR-148a-mediated anti-metastasis of hepatocellular carcinoma. Mol Carcinog. 2014;53:960\u20139.","journal-title":"Mol Carcinog"},{"key":"1649_CR36","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1002\/hep.27543","volume":"61","author":"L Li","year":"2015","unstructured":"Li L, Liu Y, Guo Y, Liu B, Zhao Y, Li P, Song F, et al. Regulatory MiR-148a-ACVR1\/BMP circuit defines a cancer stem cell-like aggressive subtype of hepatocellular carcinoma. Hepatology. 2015;61:574\u201384.","journal-title":"Hepatology"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-020-01649-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-020-01649-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-020-01649-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T19:15:44Z","timestamp":1628018144000},"score":1,"resource":{"primary":{"URL":"https:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-020-01649-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1649"],"URL":"https:\/\/doi.org\/10.1186\/s13046-020-01649-0","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,4]]},"assertion":[{"value":"13 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experiments containing patient specimens or data were approved by the Ethics Committee of Tongji Hospital, HUST and were performed in accordance with the Declaration of Helsinki Principles. Prior written and informed consent was obtained from each patient.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All materials and images are original. No consent needs to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"150"}}