Редактирование: ZEB1

Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) [AREB6] [TCF8]

==Publications==

{{medline-entry
|title=MicroRNA-338-5p plays a tumor suppressor role in glioma through inhibition of the MAPK-signaling pathway by binding to [[FOXD1]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30225541
|abstract=MicroRNAs (miRs) play an important role in many cancers and can affect cancer cell behavior, including glioma. This study aims at investigating the effects of miR-338-5p on the senescence, migration, invasion, and apoptosis of glioma cells via MAPK-signaling pathway by binding to [[FOXD1]]. Gene expression microarray analysis was performed to screen differentially expressed miRNAs associated with glioma. Glioma tissues and adjacent tissues were collected. siRNA, mimic, and inhibitor were introduced for investigating the tumor suppressor role of miR-338-5p in glioma. Proliferation, migration, invasion, senescence, cell-cycle distribution, and apoptosis after transfection were detected by MTT assay, scratch test, Transwell assay, β-galactosidase staining, and flow cytometry, respectively. [[FOXD1]] was identified as the up-regulated gene in glioma based on microarray data of GSE65626. [[FOXD1]] was the target gene of miR-338-5p. Glioma tissues had increased expression of [[FOXD1]], MEK-2, ERK-1, DAF, [[PCNA]], and Bcl-2, and decreased expression of miR-338-5p and Bax. In cell experiments, after transfected with overexpressed miR-338-5p, higher expression of miR-338-5p, Bax, CD133, [[ZEB1]], [[SOX2]], [[SNAI1]], and [[MMP2]], but lower expression of [[FOXD1]], MEK-2, ERK-1, Bcl-2, DAF, and [[PCNA]] were found accompanied with weaker proliferation, migration and invasion as well as stemness abilities but stronger senescence and higher apoptosis rate. We found that overexpression of miR-338-5p suppresses glioma cell proliferation, migration, and invasion and accelerates its senescence and apoptosis by decreasing [[FOXD1]] expression via inhibition of activation of MAPK-signaling pathway.
|mesh-terms=* Apoptosis
* Biomarkers
* Brain Neoplasms
* Cell Line, Tumor
* Cell Movement
* Cell Proliferation
* Cell Survival
* Computational Biology
* Forkhead Transcription Factors
* Gene Expression
* Gene Expression Profiling
* Gene Expression Regulation, Neoplastic
* Genes, Reporter
* Genes, Tumor Suppressor
* Glioma
* Humans
* MicroRNAs
* Mitogen-Activated Protein Kinases
* Neoplastic Stem Cells
* RNA Interference
* Signal Transduction
|keywords=* FOXD1
* Glioma cells
* Invasion
* MAPK-signaling pathway
* MicroRNA-338-5p
* Migration
* Proliferation
* Senescence
|full-text-url=https://sci-hub.do/10.1007/s00432-018-2745-y
}}
{{medline-entry
|title=Ultraviolet A irradiation induces senescence in human dermal fibroblasts by down-regulating [[DNMT1]] via [[ZEB1]].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29466247
|abstract=In this study, we report the role of DNA methyltransferase 1 ([[DNMT1]]) in ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs). We show that [[DNMT1]] expression was significantly reduced during UVA-induced senescence, and this senescence could be alleviated or aggravated by the up- or down-regulation of [[DNMT1]], respectively. Expression of the transcription factor zinc finger E-box binding homeobox 1([[ZEB1]]) also decreased after UVA irradiation, following a UVA-induced increase of intracellular reactive oxygen species (ROS). We show that [[ZEB1]] binds to the DMNT1 promoter and regulates its transcription, which, in turn, affects cellular senescence. These changes in DMNT1 and [[ZEB1]] expression following UVA exposure were confirmed in matched skin specimens that had or had not been sun-exposed. On analyzing the promoter methylation of 24 senescence associated genes in these matched skin specimens, we discovered that p53 promoter methylation was significantly reduced in sun-exposed skin. [i]In vitro[/i] experiments confirmed that UVA irradiation reduced p53 promoter methylation, and [[DNMT1]] up-regulation could reverse this effect. Collectively, down-regulation of [[ZEB1]] caused by UVA induced ROS could transcriptionally inhibit [[DNMT1]], leading to low methylation level of senescence related proteins p53 and increase its expression, eventually result in cellar senescence.
|mesh-terms=* Cellular Senescence
* Down-Regulation
* Fibroblasts
* Humans
* Reactive Oxygen Species
* Repressor Proteins
* Skin Aging
* Skin Physiological Phenomena
* Tumor Suppressor Protein p53
* Ultraviolet Rays
* Up-Regulation
* Zinc Finger E-box-Binding Homeobox 1
|keywords=* DNMT1
* UVA
* ZEB1
* methylation
* senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842848
}}
{{medline-entry
|title=p16  induces senescence and inhibits EMT through microRNA-141/microRNA-146b-5p-dependent repression of AUF1.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27596953
|abstract=Senescence and epithelial-to-mesenchymal transition (EMT) processes are under the control of common tumor suppressor proteins, EMT transcription factors, and microRNAs. However, the molecular mechanisms that coordinate the functional link between senescence and EMT are still elusive. We have shown here that p16  -related induction of senescence is mediated through miR-141 and miR-146b-5p. These two microRNAs are up-regulated in aging human fibroblast and epithelial cells. Furthermore, miR-141 and miR146b-5p trigger cell cycle arrest at G1 phase and induce senescence in primary human fibroblasts and breast cancer cells in the presence and absence of p16  . Like p16  -induced senescence, miR-141/miR146b-5p-related senescence is not associated with secretory phenotype, and is mediated through the RNA binding protein AUF1. We have further demonstrated that p16  and its downstream miRNA targets inhibit EMT through suppressing the EMT inducer [[ZEB1]] in an AUF1-dependent manner. Indeed, AUF1 binds the mRNA of this gene leading to increase in its level. These results indicate that p16  controls both senescence and EMT through repressing EMT-related transcription factor via miR-141/miR146b-5p and their target AUF1. This sheds more light on the molecular basis of the tumor suppressive functions of p16  , which represses both the proliferative and the migratory/invasive capacities of cells. © 2016 Wiley Periodicals, Inc.
|mesh-terms=* Cell Cycle
* Cell Line, Tumor
* Cell Movement
* Cell Proliferation
* Cell Survival
* Cellular Senescence
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p18
* Epithelial Cells
* Epithelial-Mesenchymal Transition
* Fibroblasts
* Gene Expression Regulation, Neoplastic
* Heterogeneous Nuclear Ribonucleoprotein D0
* Heterogeneous-Nuclear Ribonucleoprotein D
* Humans
* MicroRNAs
* Up-Regulation
|keywords=* AUF1
* EMT
* miR-141/miR-146b-5p
* p16INK4a
* senescence
|full-text-url=https://sci-hub.do/10.1002/mc.22564
}}
{{medline-entry
|title=The [[ZEB1]] transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24371144
|abstract=Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin-dependent kinase inhibitors (cdki). It is unclear how Ras causes repression of Bmi1 in primary cells to suppress tumor formation while inducing the gene in cancer cells to drive tumor progression. Ras also induces the EMT transcription factor [[ZEB1]] to trigger tumor invasion and metastasis. Beyond its well-documented role in EMT, [[ZEB1]] is important for maintaining repression of cdki. Indeed, heterozygous mutation of [[ZEB1]] is sufficient for elevated cdki expression, leading to premature senescence of primary cells. A similar phenotype is evident with Bmi1 mutation. We show that activation of Rb1 in response to mutant Ras causes dominant repression of [[ZEB1]] in primary cells, but loss of the Rb1 pathway is a hallmark of cancer cells and in the absence of such Rb1 repression Ras induces [[ZEB1]] in cancer cells. [[ZEB1]] represses miR-200 in the context of a mutual repression loop. Because miR-200 represses Bmi1, induction of [[ZEB1]] leads to induction of Bmi1. Rb1 pathway status then dictates the opposing effects of mutant Ras on the [[ZEB1]]-miR-200 loop in primary versus cancer cells. This loop not only triggers EMT, surprisingly we show it acts downstream of Ras to regulate Bmi1 expression and thus the critical decision between oncogene-induced senescence and tumor initiation. 
|mesh-terms=* Animals
* Cell Line, Tumor
* Cell Transformation, Neoplastic
* Cellular Senescence
* Gene Expression Regulation, Neoplastic
* Homeodomain Proteins
* Mice
* Mice, Inbred BALB C
* Mice, Knockout
* Mice, Nude
* MicroRNAs
* Mutation
* Neoplasms
* Oncogene Protein p21(ras)
* Polycomb Repressive Complex 1
* Proto-Oncogene Proteins
* RNA, Neoplasm
* Retinoblastoma Protein
* Transcription Factors
* Zinc Finger E-box-Binding Homeobox 1
|keywords=* Cancer
* Cancer Biology
* Cell Signaling
* Epithelial Mesenchymal Transition
* Senescence
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924277
}}