{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:06:18Z","timestamp":1789779978552,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T00:00:00Z","timestamp":1419292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"\u2018Program for New Century Excellent Talents in University\u2019 of the Ministry of Education"},{"name":"National High-tech R&D Program of China","award":["2012AA020204"],"award-info":[{"award-number":["2012AA020204"]}]},{"name":"National Science and Technology major projects","award":["2012ZX10002010-001-005"],"award-info":[{"award-number":["2012ZX10002010-001-005"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Abstract<\/jats:title>Background and Aim<\/jats:title>Our previous proteomic research found that chloride intracellular channel 1 (CLIC<\/jats:styled-content>1) was upregulated in hepatocellular carcinoma (HCC<\/jats:styled-content>) tissues with portal vein tumor thrombus. The present study aimed to determine the role of CLIC<\/jats:styled-content>1 in HCC<\/jats:styled-content> invasion.<\/jats:p><\/jats:sec>Methods<\/jats:title>Immunohistochemistry was used to explore protein expression of CLIC<\/jats:styled-content>1 in 15 cirrhotic tissues and 69 pairs of HCC<\/jats:styled-content> and paracarcinoma tissues. Small interfering RNA<\/jats:styled-content> (siRNA<\/jats:styled-content>) and plasmids were transfected into HepG2 and SMMC<\/jats:styled-content>7721 cells, and the in vitro<\/jats:italic> function of CLIC<\/jats:styled-content>1 in these cells were assessed with cell counting kit\u20108 assays, cell apoptosis assays, scratch assays, and transwell assays. Microarray analysis was also performed to further explore the candidate genes related to CLIC<\/jats:styled-content>1.<\/jats:p><\/jats:sec>Results<\/jats:title>Our results confirmed that upregulated CLIC<\/jats:styled-content>1 expression was significantly correlated with vascular invasion (P<\/jats:italic>\u2009=\u20090.034) in HCC<\/jats:styled-content> tissues. Knockdown of CLIC<\/jats:styled-content>1 decreased cell viability and the invasive potency of HepG<\/jats:styled-content>2 cells, whereas CLIC<\/jats:styled-content>1 overexpression resulted in an opposite effect in SMMC<\/jats:styled-content>7721 cells. Microarray analysis identified 618 genes that were differentially expressed (fold change \u2265\u20092, P<\/jats:italic>\u2009<\u20090.05) between HepG<\/jats:styled-content>2 cells transfected with CLIC<\/jats:styled-content>1 siRNA<\/jats:styled-content> and the negative control. Further studies indicate that knockdown of CLIC<\/jats:styled-content>1 increased maspin expression and reduced vascular endothelial growth factor (VEGF<\/jats:styled-content>), matrixmetalloproteinase\u20102 (MMP<\/jats:styled-content>2), MMP<\/jats:styled-content>9, MMP<\/jats:styled-content>11, and MMP<\/jats:styled-content>12 expression. In contrast, overexpression of CLIC<\/jats:styled-content>1 decreased maspin expression and increased VEGF<\/jats:styled-content>, MMP<\/jats:styled-content>2, MMP<\/jats:styled-content>12, and MMP<\/jats:styled-content>13 expression.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>CLIC<\/jats:styled-content>1 protein expression is significantly correlated with vascular invasion, and the present study suggests a previously unknown mechanism of CLIC<\/jats:styled-content>1\u2010mediated control of HCC<\/jats:styled-content> invasiveness by targeting maspin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12668","type":"journal-article","created":{"date-parts":[[2014,7,3]],"date-time":"2014-07-03T02:50:07Z","timestamp":1404355807000},"page":"208-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Chloride intracellular channel 1 participates in migration and invasion of hepatocellular carcinoma by targeting 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