{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:22:48Z","timestamp":1761218568816,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The underlying mechanisms of metastasis and recurrence of liver cancer remain largely unknown. Here, we found that Brother of the Regulator of Imprinted Sites (BORIS) variant SF2(C2\/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells and clinical tumor samples, related to the formation of satellite nodules. Its over expression promoted self\u2010renewal, the expression of tumor stem cell markers, chemoresistance, wound healing rate, invasion and metastasis of HepG2 and Hep3B cells; reinforced epithelial\u2010mesenchymal transition (EMT), decreased the expression of E\u2010cadherin and increased N\u2010cadherin and Vimentin. Subcellular localization experiment showed that BORIS SF2(C2\/A4) was localized in nucleus and cytoplasm. Further double luciferase reporter gene experiment confirmed that it bound to <jats:italic>TWIST1<\/jats:italic> gene promoter and significantly increased latter expression. BORIS SF2(C2\/A4) knock down induced apoptosis of HCCLM3 and PLC\/PRF\/5 cells, and increased the protein content of cleaved caspase 3. Additionally, BORIS SF2(C2\/A4) over expression increased the expression of fibroblast growth factor 2 (FGF2) in HepG2 and Hep3B cells. FGF2 expressed higher in HCC tumor tissues than in paired peri\u2010tumor tissues, and its expression was positively correlated with BORIS SF2(C2\/A4). Interestingly, high expression of FGF2 is also associated with the formation of satellite nodules. Moreover, using the medium from BORIS SF2(C2\/A4) overexpressed cell lines to coculture hepatic stellate cell (HSCs) line LX\u20102, the latter could be activated and increased the expression of CD90 and PIGF, which is consistent with the effect of adding bFGF alone. These results indicate that BORIS SF2(C2\/A4) plays a role in deterioration of liver cancer by regulating TWIST1 to induce EMT, and by FGF2 to activate HSCs.<\/jats:p>","DOI":"10.1002\/mc.23520","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T08:59:26Z","timestamp":1679043566000},"page":"731-742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BORIS variant SF2(C2\/A4) promotes the malignant development of liver cancer by activating epithelial\u2010mesenchymal transition and hepatic stellate cells"],"prefix":"10.1002","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0328-0821","authenticated-orcid":false,"given":"Ling","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longjun","family":"Xian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kefei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Liver Transplantation, West China Hospital Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Liver Transplantation, West China Hospital Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Liver Transplantation, West China Hospital Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8480-2550","authenticated-orcid":false,"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery Division of Liver Transplantation, West China Hospital Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2762-1179","authenticated-orcid":false,"given":"Yang","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences &amp; Forensic Medicine Sichuan University Chengdu Sichuan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.04.061"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.50"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-019-0150-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006420"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.06.017"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2011.05.007"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013872"},{"key":"e_1_2_10_9_1","first-page":"6","article-title":"BORIS\/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer","volume":"13","author":"Link PA","year":"2013","journal-title":"Cancer Immun"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7165"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171460"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0700-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01539-x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3447"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.05.031"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0533-1"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.022"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.08.014"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1196-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5460rev"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz134"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3282"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12465"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6839"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-013-1547-5"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07509"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.259"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-1-r9"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08909"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.03.027"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.189"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2012.04.016"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-10-0463"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2012.06.003"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2011.378"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26346"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.8998"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.15.3023"},{"issue":"1","key":"e_1_2_10_40_1","article-title":"MAGEA1 inhibits the expression of BORIS via increased promoter methylation","volume":"132","author":"Zhao J","year":"2019","journal-title":"J Cell Sci"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40786"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23520","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.23520","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23520","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T16:57:29Z","timestamp":1692723449000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.23520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/mc.23520"],"URL":"https:\/\/doi.org\/10.1002\/mc.23520","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"type":"print","value":"0899-1987"},{"type":"electronic","value":"1098-2744"}],"subject":[],"published":{"date-parts":[[2023,3,17]]},"assertion":[{"value":"2022-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}