EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling

Pang, Bo; Zheng, Xiangrong; Tian, Jingxia; Gao, Taihong; Gu, Guangyan; Zhang, Rui; Fu, Yan; Pang, Qi; Li, Xingang; Liu, Qian

doi:10.18632/oncotarget.9761

Cited by 46 publications

(50 citation statements)

References 37 publications

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“…The following are the siRNA sequences were synthesized targeting human MOB1: sequence 1: 5′-AUG AAU GGG UUG CAG UUA A-3′; sequence 2: 5′-GCA GAU GGA ACG AAC AUA A-3′. ShRNA constructs with the target sequences of KDM2B sequence 1:5′-GAT GAG CAT GTC CCA GTT T-3′; sequence 2: 5′-TGA GCG TGA AAG GTT GTT T-3′were reported previously [18,31,32]. Each amplified DNA fragment was verified by sequencing the inserts and flanking regions of the plasmids.…”

Section: Plasmids and Short Hairpin Rnas (Shrna)mentioning

confidence: 99%

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Quan

Chen

Jiao

et al. 2020

J Exp Clin Cancer Res

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Background: Mps1 binding protein (MOB1) is one of the core components of the mammalian Hippo pathway and plays important roles in cancer development. However, its expression, function and regulation in pancreatic ductal adenocarcinoma (PDAC) have not been revealed yet. Methods: The expression of MOB1 and lysine demethylase 2B (KDM2B) in PDAC and adjacent normal pancreas tissues were measured. Also, the underlying mechanisms of altered MOB1 expression and its impact on PDAC biology were investigated. Results: We revealed for the first time that MOB1 was decreased expression in PDAC and was a statistically significant independent predictor of poor survival, and restored expression of MOB1 suppressed the proliferation, migration and invasion of PDAC cells. Further studies demonstrated that KDM2B directly bound to the promoter region of MOB1, and suppressed the promoter activity of MOB1 and transcriptionally inhibited the MOB1 expression. Furthermore, KDM2B regulated Hippo pathway and promoted PDAC proliferation, migration and invasion via MOB1. Conclusion: This study demonstrated the mechanism and roles of a novel KDM2B/MOB1/Hippo signaling in PDAC progression.

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Section: Plasmids and Short Hairpin Rnas (Shrna)mentioning

confidence: 99%

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Quan

Chen

Jiao

et al. 2020

J Exp Clin Cancer Res

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“…Enhancer of zeste 2 polycomb repressive complex 2 (EZH2), a multifaceted oncogenic protein, promotes glioblastoma tumorigenesis and malignant progression through activation of HIF-1α and the Warburg effect. HIF-1α activation is necessary for EZH2-mediated metabolic adaption 22 . Ribosomal protein S7 (RPS7) inhibits glycolysis in colorectal cancer by suppressing the expression of HIF-1α as well as of GLUT4 and lactate dehydrogenase B (LDHB) 23 .…”

Section: Master Regulator Hif-1αmentioning

confidence: 99%

The Glycolytic Switch in Tumors: How Many Players Are Involved?

et al. 2017

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Reprogramming of cellular metabolism is a hallmark of cancers. Cancer cells more readily use glycolysis, an inefficient metabolic pathway for energy metabolism, even when sufficient oxygen is available. This reliance on aerobic glycolysis is called the Warburg effect, and promotes tumorigenesis and malignancy progression. The mechanisms of the glycolytic shift in tumors are not fully understood. Growing evidence demonstrates that many signal molecules, including oncogenes and tumor suppressors, are involved in the process, but how oncogenic signals attenuate mitochondrial function and promote the switch to glycolysis remains unclear. Here, we summarize the current information on several main mediators and discuss their possible mechanisms for triggering the Warburg effect.

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“…During the process of tumor evolution, Hif-1α may promote tumor cell proliferation and angiogenesis, and may cause tumor recurrence and metastasis (15). There is interactive regulation among Hif-1α and Wnt/β-catenin signalling molecules (16) and EZH2 in glioblastoma (17,18). In the present study, DZNep was used to observe the effect of DZNep on the proliferation, apoptosis, invasion and metastasis of BGC-823 gastric cancer cells, and to investigate the function of DZNep in the regulation of Hif-1α and Wnt/β-catenin signalling molecules via the inhibition of EZH2.…”

Section: Introductionmentioning

confidence: 99%

DZNep inhibits Hif‑1α and Wnt signalling molecules to attenuate the proliferation and invasion of BGC‑823 gastric cancer cells

et al. 2019

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3-deazaneplanocin A (DZNep) is a histone methyltransferase inhibitor, which may cause the reactivation of silenced tumor suppressor genes in tumors to inhibit the development, metastasis and dissemination of tumor cells. However, the effects and mechanisms of its application in gastric cancer remain unclear. The present study revealed an inhibitory function of DZNep in BGC-823 cells. The cell colony, Cell Counting Kit-8 (CCK8), wound healing, Transwell and flow cytometry assays were performed, and the results demonstrated that DZNep could inhibit the proliferation, apoptosis and invasion of BGC-823 cells, and promote their apoptosis. The effects of intervention in BDC-823 cells with DZNep on the RNA and protein expression levels of hypoxia-inducible factor (Hif-1α) and Wnt/β-catenin signalling molecules were further examined using reverse transcription-quantitative PCR and western blot analysis. The results demonstrated that different concentrations of DZNep could inhibit the expression of enhancer of zeste homolog 2 (EZH2) protein, decrease the RNA and protein expression levels of Hif-1α, total β-catenin and phosphorylated-β-catenin and increase the expression levels of non-phosphorylated-β-catenin to different degrees. The results of the present study suggests that DZNep inhibits BGC-823 gastric cancer cells via the inhibition of EZH2, Hif-1α and Wnt/β-catenin signalling molecules. These results provide theoretical basis for the application of DZNep in clinical trials.

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EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling

Cited by 46 publications

References 37 publications

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

Lysine demethylase 2 (KDM2B) regulates hippo pathway via MOB1 to promote pancreatic ductal adenocarcinoma (PDAC) progression

The Glycolytic Switch in Tumors: How Many Players Are Involved?

DZNep inhibits Hif‑1α and Wnt signalling molecules to attenuate the proliferation and invasion of BGC‑823 gastric cancer cells

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