Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep19943
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dc.titleGRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification
dc.contributor.authorChung, V.Y
dc.contributor.authorTan, T.Z
dc.contributor.authorTan, M
dc.contributor.authorWong, M.K
dc.contributor.authorKuay, K.T
dc.contributor.authorYang, Z
dc.contributor.authorYe, J
dc.contributor.authorMuller, J
dc.contributor.authorKoh, C.M
dc.contributor.authorGuccione, E
dc.contributor.authorThiery, J.P
dc.contributor.authorHuang, R.Y.-J
dc.date.accessioned2020-09-02T06:58:26Z
dc.date.available2020-09-02T06:58:26Z
dc.date.issued2016
dc.identifier.citationChung, V.Y, Tan, T.Z, Tan, M, Wong, M.K, Kuay, K.T, Yang, Z, Ye, J, Muller, J, Koh, C.M, Guccione, E, Thiery, J.P, Huang, R.Y.-J (2016). GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification. Scientific Reports 6 : 19943. ScholarBank@NUS Repository. https://doi.org/10.1038/srep19943
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174023
dc.description.abstractEpithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, has been implicated to contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). Here we report that a transcription factor-Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. EOC tumours with lower GRHL2 levels are associated with the Mes/Mesenchymal molecular subtype and a poorer overall survival. shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype results in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, microRNA-200b/a is identified as the direct transcriptional target of GRHL2 and regulates the epithelial status of EOC through ZEB1 and E-cadherin. Our study demonstrates that loss of GRHL2 increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding sites at miR-200b/a and E-cadherin genes. These findings support GRHL2 as a pivotal gatekeeper of EMT in EOC via miR-200-ZEB1.
dc.sourceUnpaywall 20200831
dc.subjectDNA binding protein
dc.subjectGRHL2 protein, human
dc.subjecthistone
dc.subjectmicroRNA
dc.subjectMIRN200 microRNA, human
dc.subjectRNA
dc.subjecttranscription factor
dc.subjecttranscription factor ZEB1
dc.subjecttumor protein
dc.subjectZEB1 protein, human
dc.subjectDNA responsive element
dc.subjectepithelial mesenchymal transition
dc.subjectfemale
dc.subjectgenetic transcription
dc.subjectgenetics
dc.subjecthuman
dc.subjectmetabolism
dc.subjectovary tumor
dc.subjectpathology
dc.subjectprotein processing
dc.subjecttumor cell line
dc.subjectCell Line, Tumor
dc.subjectDNA-Binding Proteins
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectFemale
dc.subjectHistones
dc.subjectHumans
dc.subjectMicroRNAs
dc.subjectNeoplasm Proteins
dc.subjectOvarian Neoplasms
dc.subjectProtein Processing, Post-Translational
dc.subjectResponse Elements
dc.subjectRNA, Neoplasm
dc.subjectTranscription Factors
dc.subjectTranscription, Genetic
dc.subjectZinc Finger E-box-Binding Homeobox 1
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.description.doi10.1038/srep19943
dc.description.sourcetitleScientific Reports
dc.description.volume6
dc.description.page19943
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