ZEB1 regulates glioma stemness through LIF repression
| Autor: | Benjamin R. Uy, Minlin Xu, Rachel Jung, Mitch Hymowitz, John S. Yu, Minzhi Liu, Lincoln A. Edwards, Wei Zhang, Keith L. Black, Dror Berel, Xuemo Fan, Nam-Ho Kim, Aiguo Li, Altan Rentsendorj, Mecca Madany |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Gene Dosage Biology Gene dosage Leukemia Inhibitory Factor Article 03 medical and health sciences Cancer stem cell Glioma medicine Humans Psychological repression Regulation of gene expression Gene knockdown Multidisciplinary Zinc Finger E-box-Binding Homeobox 1 medicine.disease Survival Analysis 3. Good health Repressor Proteins 030104 developmental biology Gene Expression Regulation Cancer research Medicine Stem cell Neoplasm Grading Leukemia inhibitory factor Gene Deletion Protein Binding |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-00106-x |
| Popis: | The identification of a stem cell regulatory gene which is aberrantly expressed in glioma and associated with patient survival would increase the understanding of the role of glioma cancer stem cells (GCSCs) in the virulence of gliomas. Interrogating the genomes of over 4000 brain cancers we identified ZEB1 deletion in ~15% (grade II and III) and 50% of glioblastomas. Meta-analysis of ZEB1 copy number status in 2,988 cases of glioma revealed disruptive ZEB1 deletions associated with decreased survival. We identified ZEB1 binding sites within the LIF (stemness factor) promoter region, and demonstrate LIF repression by ZEB1. ZEB1 knockdown in GCSCs caused LIF induction commensurate with GCSC self-renewal and inhibition of differentiation. IFN-γ treatment to GCSCs induced ZEB1 expression, attenuating LIF activities. These findings implicate ZEB1 as a stem cell regulator in glioma which when deleted leads to increased stemness, tumorigenicity and shortened patient survival. |
| Databáze: | OpenAIRE |
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