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Article: Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines

TitleEpigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2013, v. 8 n. 9, p. Article no. e72435 How to Cite?
AbstractActivation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+high cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+high cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression. © 2013 Wang et al.
Persistent Identifierhttp://hdl.handle.net/10722/191274
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, X-
dc.contributor.authorNg, RK-
dc.contributor.authorMing, X-
dc.contributor.authorZhang, W-
dc.contributor.authorChen, L-
dc.contributor.authorChu, ACY-
dc.contributor.authorPang, RWC-
dc.contributor.authorLo, CM-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLiu, X-
dc.contributor.authorPoon, RTP-
dc.contributor.authorFan, ST-
dc.date.accessioned2013-10-15T06:51:38Z-
dc.date.available2013-10-15T06:51:38Z-
dc.date.issued2013-
dc.identifier.citationPLoS One, 2013, v. 8 n. 9, p. Article no. e72435-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/191274-
dc.description.abstractActivation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+high cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+high cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression. © 2013 Wang et al.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleEpigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines-
dc.typeArticle-
dc.identifier.emailWang, X: xqwang@hku.hk-
dc.identifier.emailNg, RK: raykitng@hku.hk-
dc.identifier.emailMing, X: mingxy@hku.hk-
dc.identifier.emailChen, L: chenlin@hku.hk-
dc.identifier.emailPang, RWC: robertap@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLiu, X: xqliu@hku.hk-
dc.identifier.emailPoon, RTP: poontp@hku.hk-
dc.identifier.emailFan, ST: stfan@hku.hk-
dc.identifier.authorityWang, X=rp00507-
dc.identifier.authorityNg, RK=rp00273-
dc.identifier.authorityPang, RWC=rp00274-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityPoon, RTP=rp00446-
dc.identifier.authorityFan, ST=rp00355-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0072435-
dc.identifier.pmid24023739-
dc.identifier.scopuseid_2-s2.0-84883358002-
dc.identifier.hkuros225664-
dc.identifier.volume8-
dc.identifier.issue9-
dc.identifier.spageArticle no. e72435-
dc.identifier.epageArticle no. e72435-
dc.identifier.isiWOS:000324515600019-
dc.publisher.placeUnited States-

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