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Article: KIFC1 is activated by TCF-4 and promotes hepatocellular carcinoma pathogenesis by regulating HMGA1 transcriptional activity

TitleKIFC1 is activated by TCF-4 and promotes hepatocellular carcinoma pathogenesis by regulating HMGA1 transcriptional activity
Authors
KeywordsHMGA1
Hepatocellular carcinoma
Kinesin family member C1
Pathogenesis
TCF-4
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home
Citation
Journal of Experimental and Clinical Cancer Research, 2019, v. 38 n. 1, p. article no. 329 How to Cite?
AbstractBACKGROUND: Kinesins play important roles in the development and progression of many human cancers. The functions and underlying mechanisms of kinesin family member C1 (KIFC1), a member of the kinesin-14 family, in the pathogenesis of hepatocellular carcinoma (HCC) have not been fully elucidated. METHODS: In this study, 168 HCC samples were first analyzed to examine the association between KIFC1 expression and patient clinicopathological features and prognosis. The role of KIFC1 in HCC cell proliferation and metastasis was investigated both in vivo and in vitro. The upstream regulation and downstream targets of KIFC1 were studied by qRT-PCR, western blotting, coimmunoprecipitation, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: KIFC1 was highly expressed in HCC tissues and positively associated with advanced stages and poor prognosis. KIFC1 knockdown suppressed HCC cell proliferation and invasion both in vitro and in vivo. Furthermore, KIFC1 knockdown decreased invadopodia formation and reduced epithelial-mesenchymal transition (EMT). HMGA1, an architectural transcriptional factor, was identified to interact with KIFC1. HMGA1 could bind to the promoters of Stat3, MMP2 and EMT-related genes and promote gene transcription. KIFC1 enhanced HMGA1 transcriptional activity and facilitated HCC proliferation and invasion. Moreover, KIFC1 was activated by TCF-4, and KIFC1 inhibition enhanced HCC cell sensitivity to paclitaxel. CONCLUSIONS: Our findings suggest that KIFC1, activated by TCF-4, functions as an oncogene and promotes HCC pathogenesis through regulating HMGA1 transcriptional activity and that KIFC1 is a potential therapeutic target to enhance the paclitaxel sensitivity of HCC.
Persistent Identifierhttp://hdl.handle.net/10722/278128
ISSN
2018 Impact Factor: 5.646
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorTeng, K-
dc.contributor.authorWei, S-
dc.contributor.authorZhang, C-
dc.contributor.authorChen, J-
dc.contributor.authorChen, J-
dc.contributor.authorXiao, K-
dc.contributor.authorLiu, J-
dc.contributor.authorDai, M-
dc.contributor.authorGuan, X-
dc.contributor.authorYun, J-
dc.contributor.authorXie, D-
dc.date.accessioned2019-10-04T08:08:02Z-
dc.date.available2019-10-04T08:08:02Z-
dc.date.issued2019-
dc.identifier.citationJournal of Experimental and Clinical Cancer Research, 2019, v. 38 n. 1, p. article no. 329-
dc.identifier.issn1756-9966-
dc.identifier.urihttp://hdl.handle.net/10722/278128-
dc.description.abstractBACKGROUND: Kinesins play important roles in the development and progression of many human cancers. The functions and underlying mechanisms of kinesin family member C1 (KIFC1), a member of the kinesin-14 family, in the pathogenesis of hepatocellular carcinoma (HCC) have not been fully elucidated. METHODS: In this study, 168 HCC samples were first analyzed to examine the association between KIFC1 expression and patient clinicopathological features and prognosis. The role of KIFC1 in HCC cell proliferation and metastasis was investigated both in vivo and in vitro. The upstream regulation and downstream targets of KIFC1 were studied by qRT-PCR, western blotting, coimmunoprecipitation, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: KIFC1 was highly expressed in HCC tissues and positively associated with advanced stages and poor prognosis. KIFC1 knockdown suppressed HCC cell proliferation and invasion both in vitro and in vivo. Furthermore, KIFC1 knockdown decreased invadopodia formation and reduced epithelial-mesenchymal transition (EMT). HMGA1, an architectural transcriptional factor, was identified to interact with KIFC1. HMGA1 could bind to the promoters of Stat3, MMP2 and EMT-related genes and promote gene transcription. KIFC1 enhanced HMGA1 transcriptional activity and facilitated HCC proliferation and invasion. Moreover, KIFC1 was activated by TCF-4, and KIFC1 inhibition enhanced HCC cell sensitivity to paclitaxel. CONCLUSIONS: Our findings suggest that KIFC1, activated by TCF-4, functions as an oncogene and promotes HCC pathogenesis through regulating HMGA1 transcriptional activity and that KIFC1 is a potential therapeutic target to enhance the paclitaxel sensitivity of HCC.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home-
dc.relation.ispartofJournal of Experimental and Clinical Cancer Research-
dc.rightsJournal of Experimental and Clinical Cancer Research. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectHMGA1-
dc.subjectHepatocellular carcinoma-
dc.subjectKinesin family member C1-
dc.subjectPathogenesis-
dc.subjectTCF-4-
dc.titleKIFC1 is activated by TCF-4 and promotes hepatocellular carcinoma pathogenesis by regulating HMGA1 transcriptional activity-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13046-019-1331-8-
dc.identifier.pmid1340839-
dc.identifier.pmcidPMC6657086-
dc.identifier.scopuseid_2-s2.0-85070504050-
dc.identifier.hkuros306350-
dc.identifier.volume38-
dc.identifier.issue1-
dc.identifier.spagearticle no. 329-
dc.identifier.epagearticle no. 329-
dc.identifier.isiWOS:000477016600002-
dc.publisher.placeUnited Kingdom-
dc.relation.erratumdoi:10.1186/s13046-019-1460-0-
dc.identifier.issnl1756-9966-

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