{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:55:09Z","timestamp":1782125709398,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91440203"],"award-info":[{"award-number":["91440203"]}],"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":["81502433"],"award-info":[{"award-number":["81502433"]}],"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":["31620103910"],"award-info":[{"award-number":["31620103910"]}],"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":["31601021"],"award-info":[{"award-number":["31601021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Gallbladder cancer (<jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>) is the most common malignant tumor of the biliary tract system. Epithelial\u2013mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>) plays a vital role in the process of tumor metastasis. Mesenchymal\u2010like cells can serve as a source of cancer stem cells, which can confer the <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> phenotype. Placental growth factor (<jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content>) belongs to the vascular endothelial growth factor family and plays a vital role in cancer. However, the underlying molecular mechanisms about the influence of <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> on <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> remain unknown. Here we show that <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> expression levels were higher in <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> tissues than in normal adjacent tissues and were associated with poor prognosis in <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> patients. Exogenous <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> enhanced the migration, invasion, and tumorsphere formation of <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> cells. Conversely, knockdown of <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> decreased the aggressive phenotype of <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> cells. Mechanistically, exogenous <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> upregulated micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u201019a (miR\u201019a) expression through the activation of c\u2010<jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>. Moreover, Spearman's correlation analysis showed a positive pairwise correlation among <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content>, c\u2010<jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>, and miR\u201019a expression in <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content> tissues. Taken together, these results suggest that <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> promotes <jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content> and tumorsphere formation through inducing miR\u201019a expression by upregulating c\u2010<jats:styled-content style=\"fixed-case\">MYC<\/jats:styled-content>. Thus, <jats:styled-content style=\"fixed-case\">PLGF<\/jats:styled-content> could be a promising molecular therapeutic target for <jats:styled-content style=\"fixed-case\">GBC<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cas.13585","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T07:11:29Z","timestamp":1521961889000},"page":"1532-1544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The <scp>PLGF<\/scp>\/c\u2010<scp>MYC<\/scp>\/miR\u201019a axis promotes metastasis and stemness in gallbladder cancer"],"prefix":"10.1111","volume":"109","author":[{"given":"Huaifeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunping","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shili","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangsong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6110-0185","authenticated-orcid":false,"given":"Yingbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China"},{"name":"Institute of Biliary Tract Disease Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201744147"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3030"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.146"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2010.09.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-3292-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13248"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2672"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.11.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.028"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01106"},{"key":"e_1_2_8_12_1","first-page":"1733","article-title":"The tumor microenvironment in hepatocellular carcinoma (review)","volume":"40","author":"Leonardi GC","year":"2012","journal-title":"Int J Oncol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i43.12211"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.948420"},{"key":"e_1_2_8_15_1","first-page":"8506","article-title":"Placenta growth factor promotes migration through regulating epithelial\u2010mesenchymal transition\u2010related protein expression in cervical cancer","volume":"7","author":"Huang W","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.05.020"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.07.022"},{"key":"e_1_2_8_18_1","first-page":"4953","article-title":"Prognostic significance of plasma placental growth factor levels in renal cell cancer: an association with clinical characteristics and vascular endothelial growth factor levels","volume":"23","author":"Matsumoto K","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7819-3-68"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.03.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0258-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-013-9653-x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12616"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.257"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2012.08.014"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3452"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0527"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0625-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.125"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03677"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11602"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2014.07.002"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201540678"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21831"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.313"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0616-z"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065217"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.311"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-014-0311-8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1009009107"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a014175"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947601910377488"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1861409"},{"key":"e_1_2_8_45_1","first-page":"1624","article-title":"Expression, regulation and mechanism of action of the miR\u201017\u201092 cluster in tumor cells (Review)","volume":"40","author":"Fang LL","year":"2017","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5167"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2017.02.020"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.110"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2015.76"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3299-3_15"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13585","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13585","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.13585","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T04:04:40Z","timestamp":1693713880000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/cas.13585"],"URL":"https:\/\/doi.org\/10.1111\/cas.13585","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,27]]},"assertion":[{"value":"2017-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}