Dataset Information


Grainyhead-like 2 (GRHL2) maintains the epithelial status of ovarian cancer through miR-200-ZEB1 regulatory networks (expression)

ABSTRACT: Epithelial ovarian cancer (EOC) is clinically heterogeneous, comprising different histological and biological subtypes. Multiple studies have implicated epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, to contribute significantly to this molecular heterogeneity of EOC. From gene expression analyses of a collection of EMT-characterized EOC cell lines, we found that the expression of the transcription factor Grainyhead-like 2 (GRHL2) correlates with E-cadherin expression and the epithelial phenotype. EOC tumors with lower levels of GRHL2 are associated with the Mes (mesenchymal) molecular subtype and show poorer overall survival in patients. Here, we demonstrate that shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype resulted in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, we identified a variety of target genes regulated by GRHL2, including protein-coding and non-coding genes. Our data suggest that GRHL2 maintains the epithelial phenotype of EOC cells through the regulatory networks of miR-200b/a, ZEB1 and E-cadherin. These findings support GRHL2 as a crucial player in the molecular heterogeneity of EOC. 7 samples were analyzed (shNon control in duplicates; shGRHL2 #10 in duplicates, shGRHL2 #12 in triplicates)


ORGANISM(S): Homo sapiens  

SUBMITTER: Meng-Kang Wong   Ruby-Yun-Ju Huang  Julius Muller  Tuan Zea Tan  Tuan-Zea Tan  Jean-Paul Thiery  Ming Tan  Kuee-Theng Kuay  Vin-Yee Chung  Zhe Yang  Cheryl-Mei-Yi Koh  Ernesto Guccione  Jieru Ye 

PROVIDER: E-GEOD-71017 | ArrayExpress | 2016-02-25



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GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification.

Chung Vin Yee VY   Tan Tuan Zea TZ   Tan Ming M   Wong Meng Kang MK   Kuay Kuee Theng KT   Yang Zhe Z   Ye Jieru J   Muller Julius J   Koh Cheryl M CM   Guccione Ernesto E   Thiery Jean Paul JP   Huang Ruby Yun-Ju RY  

Scientific reports 20160218

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 GRHL  ...[more]

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