Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep19943
Title: GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification
Authors: Chung, 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 
Keywords: DNA binding protein
GRHL2 protein, human
histone
microRNA
MIRN200 microRNA, human
RNA
transcription factor
transcription factor ZEB1
tumor protein
ZEB1 protein, human
DNA responsive element
epithelial mesenchymal transition
female
genetic transcription
genetics
human
metabolism
ovary tumor
pathology
protein processing
tumor cell line
Cell Line, Tumor
DNA-Binding Proteins
Epithelial-Mesenchymal Transition
Female
Histones
Humans
MicroRNAs
Neoplasm Proteins
Ovarian Neoplasms
Protein Processing, Post-Translational
Response Elements
RNA, Neoplasm
Transcription Factors
Transcription, Genetic
Zinc Finger E-box-Binding Homeobox 1
Issue Date: 2016
Citation: Chung, 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
Abstract: Epithelial-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.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174023
ISSN: 20452322
DOI: 10.1038/srep19943
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