Histone demethylase KDM5A inhibits glioma cells migration and invasion by down regulating ZEB1

Dai, Bin; Huang, Hui; Guan, Feng; Zhu, Guangtong; Xiao, Zhiyong; Mao, Beibei; Su, Housheng; Hu, Zhiqiang

doi:10.1016/j.biopha.2018.01.020

Cited by 24 publications

(12 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histone H3 lysine 4 trimethylation (H3K4me3) at the promoter region of genes fulfils a key role in the regulation of transcriptional activation. Lysine demethylase 5A (KDM5A), a member of histone demethylase and the most abundant KDM5 family member, is capable of removing tri-and dimethyl marks of Histone H3 lysine 4, which has been reported to inhibit the migration and invasion of glioma cells [19]. More importantly, KDM5A is believed to be sensitive to hypoxia at the cellular level and controls a variety of cellular responses [10].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner

Peng

Zhu

et al. 2021

Clin Epigenet

View full text Add to dashboard Cite

Background Hypoxia is a characteristic of the tumor microenvironments within pancreatic cancer (PC), which has been linked to its malignancy. Recently, hypoxia has been reported to regulate the activity of important carcinogenic pathways by changing the status of histone modification. NOX4, a member of NADPH oxidase (NOX), has been found to be activated by hypoxia and promote cancer progression in several cancers. But whether it is involved in the epigenetic changes of tumor cells induced by hypoxia is still unclear, and its biological roles in PC also need to be explored. Methods A hypoxic-related gene signature and its associated pathways in PC were identified by analyzing the pancreatic cancer gene expression data from GEO and TCGA database. Candidate downstream gene (NOX4), responding to hypoxia, was validated by RT-PCR and western blot. Then, we evaluated the relationship between NOX4 expression and clinicopathologic parameters in 56 PC patients from our center. In vitro and in vivo assays were preformed to explore the phenotype of NOX4 in PC. Immunofluorescence, western blot and chromatin immunoprecipitation assays were further applied to search for a detailed mechanism. Results We quantified hypoxia and developed a hypoxia signature, which was associated with worse prognosis and elevated malignant potential in PC. Furthermore, we found that NADPH oxidase 4 (NOX4), which was induced by hypoxia and upregulated in PC in a HIF1A-independent manner, caused inactivation of lysine demethylase 5A (KDM5A), increased the methylation modification of histone H3 and regulated the transcription of EMT-associated gene_ snail family transcriptional repressor 1 (SNAIL1). This served to promote the invasion and metastasis of PC. NOX4 deficiency repressed hypoxia-induced EMT, reduced expression of H3K4ME3 and impaired the invasion and metastasis of PC cells; however, knockdown of KDM5A reversed the poor expression of H3KEME3 induced by NOX4 deficiency, thereby promoting EMT. Conclusions This study highlights the prognostic role of hypoxia-related genes in PC and strong correlation with EMT pathway. Our results also creatively discovered that NOX4 was an essential mediator for hypoxia-induced histone methylation modification and EMT in PC cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner

Peng

Zhu

et al. 2021

Clin Epigenet

View full text Add to dashboard Cite

show abstract

“…At the forefront of the ZEB1 dichotomy is the role of ZEB1 in glioblastomas. For example, Dai et al indicated that the histone demethylase KDM5A could suppress ZEB1 activity leading to decreased invasion with an implication that patient survival is shorter with increased ZEB1 expression (16). Similarly, long non-coding RNAs of antisense ZEB1 (ZEB1-AS1) which upregulate ZEB1 was shown to correlate with shorter patient survival (17).…”

Section: Introductionmentioning

confidence: 99%

ZEB1 Is a Transcription Factor That Is Prognostic and Predictive in Diffuse Gliomas

et al. 2019

View full text Add to dashboard Cite

Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens.Methods: ZEB1 alterations were retrospectively identified from a cohort of 1,160 diffuse glioma patients. Epigenome-wide association scans (EWAS) were performed on available data. We determined the utility of ZEB1 as a prognostic indicator of patient survival in diffuse gliomas and assessed the value of ZEB1 to predict the efficacy of treating diffuse glioma patients with procarbazine, CCNU, and vincristine along with radiation at diagnosis. Decision curve analysis (DCA) was used to determine if ZEB1 added benefit to clinical decision-making over and above conventional methods.Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 deletion was associated with poor overall survival (OS) with and without adjustment for age and tumor grade (adjusted HR: 4.25; 95% CI: 2.35 to 7.66; P < 0.001). Decision curve analysis confirmed that ZEB1 status with or without IDH1 was more beneficial to clinical decision making than conventional information such as age and tumor grade. We showed that ZEB1 regulates TERT expression, and patients with ZEB1 deletions likely subsume patients with mutant TERT expression in diffuse gliomas. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment.Conclusion: We demonstrate the prognostic value of ZEB1 in diffuse glioma patients. We further determine ZEB1 to be a vital and influential molecular marker in clinical decisions that exceed conventional methods regarding whether to treat or not treat patients with diffuse glioma.

show abstract

“…Table 4 illustrates that the EBV epitope-derived pentapeptides are widespread among the most disparate human proteins able to cause, when altered, a vast spectrum of diseases, from diabetes and sterility to myocarditis and death, 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 the latter two being possibly associated with the Titin imposing peptide sharing (250 shared pentapeptides).…”

Section: Resultsmentioning

confidence: 99%

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

Kanduc

Shoenfeld

2020

Global Medical Genetics

View full text Add to dashboard Cite

Sequence analyses highlight a massive peptide sharing between immunoreactive Epstein-Barr virus (EBV) epitopes and human proteins that—when mutated, deficient or improperly functioning—associate with tumorigenesis, diabetes, lupus, multiple sclerosis, rheumatoid arthritis, and immunodeficiencies, among others. Peptide commonality appears to be the molecular platform capable of linking EBV infection to the vast EBV-associated diseasome via cross-reactivity and questions the hypothesis of the “negative selection” of self-reactive lymphocytes. Of utmost importance, this study warns that using entire antigens in anti-EBV immunotherapies can associate with autoimmune manifestations and further supports the concept of peptide uniqueness for designing safe and effective anti-EBV immunotherapies.

show abstract

Histone demethylase KDM5A inhibits glioma cells migration and invasion by down regulating ZEB1

Cited by 24 publications

References 23 publications

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner

Hypoxia promotes the metastasis of pancreatic cancer through regulating NOX4/KDM5A-mediated histone methylation modification changes in a HIF1A-independent manner

ZEB1 Is a Transcription Factor That Is Prognostic and Predictive in Diffuse Gliomas

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

Contact Info

Product

Resources

About