Hypoxia stimulates neural stem cell proliferation by increasing HIF"‘1Î± expression and activating Wnt/Î²-catenin signaling

Qi, Cunfang; Zhang, J; Chen, X; Wan, Jieru; Wang, Jian; Zhang, P; Liu, Y

doi:10.14715/cmb/2017.63.7.2

Cited by 62 publications

(59 citation statements)

References 52 publications

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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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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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“…The number of dopaminergic neuron differentiated of HIF-1α knockout mNPCs was also markedly decreased [21]. Further, over-expression of HIF-1α could stimulate NSC proliferation by activating the Wnt/β-catenin signaling pathway [22]. Increase in HIF-1α and VEGF expression promoted the proliferation and differentiation of NPCs and functional recovery following cerebral ischemia [23][24].…”

Section: Discussionmentioning

confidence: 99%

Potential role of heat shock protein 90 in regulation of hyperthermia-driven differentiation of neural stem cells

Wang

Zhuo

et al. 2019

Preprint

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Objective: Our previous studies indicated that hyperthermia may play a role in differentiation of neural stem cells and that hypoxia inducible factor-1(HIF-1) was critical in this process. Heat shock protein 90 (Hsp90) is one of the most common heat-related proteins and involved in HIF-1 expression by regulating its activity and stabilization. Here, we hypothesized that HSP90 may be involved in regulation of hyperthermia-driven differentiation of neural stem cells(NSCs). We also investigated whether the HSP90 activity exert its regulatory action via HIF-1 pathway and the transcriptional level of the target genes of HIF-1. Method: The cultured NSCs were divided into three groups: an hyperthermic treatment group(40NSC) which NSCs was induced under 40˚C temperature; a control group(37NSC) which NSCs was induced under 37˚C temperature; an hyperthermic treatment and HSP90-inhibited group(40NSC+GA) which NSCs was induced with 0.5μM HSP90 inhibitor Geldanamycin(GA) under 40˚C temperature. We examined cells HSPɑ and HIF-1ɑ expression during a time window of 5 days(12h, 1d, 3d, 5d) post-differentiation. The expression HSPα, HIF-1α, VEGF (vascular endothelial growth factor) and erythmpoietin(EPO) of during a time window was evaluated by RT-qPCR. The proportion of Tuj-1 positive differentiated cells were observed by flow cytometry. Result: Hyperthermia promoted neuronal differentiation of NSC, and this effect could be blocked by HSP90 inhibitor GA. We observed the up-regulation of HSP90 during hyperthermia treatment, and that the protein levels of HIF-1α changed depending of the GA treatment. GA could not inhibited HSP90α expression but suppressed HSP activity and decreased the expression HIF-1α protein. Inhibition of HIF-1α expression by GA could consequently affect expression of its targeted genes such as VEGF and EPO. Conclusion: Hyperthermia promote differentiation of NSCs into neurons.HSP90 involved in the regulation of hyperthermia-driven differentiation of NSC, and the mechanism is related to HIF-1α and its downstream gene activation.

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“…Expression levels of LEF1 and β-catenin mRNA, nuclear mediators of wnt signaling, were also decreased following treatment with 2 mM VPA. LEF1 and β-catenin have been shown to increase cell proliferation in the developing brain of the mouse and neural stem cell [10] [11] [14]. In addition, a previous research has shown that VPA increases hsp70 protein levels in the rat cortical neurons [15].…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Decreases Cell Proliferation and Color Preference in the Zebrafish Larvae

Lee¹,

Lee²,

Choi³

et al. 2017

JBM

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Valproic acid (VPA) is widely used as an antiepileptic drug or mood stabilizer. In this study, we evaluated the effects of treatment with 2 mM VPA for 3 h on cell proliferation in the telencephalic area of zebrafish larvae using bromodeoxyuridine (BRDU) to label dividing cells. It was demonstrated that 2 mM VPA exposure for 3 h at 2 and 3 days post-fertilization (dpf) larvae decreased cell proliferation in the telencephalic area of 5 dpf larvae. The reduced cell proliferation was not restored at 10 dpf larvae. The quantitative real-time PCR (qRT-PCR) data indicated that mRNA expression levels of WNT signaling pathway-related factors such as β-catenin, LEF1, and gsk3β were altered in the zebrafish larvae treated with 2 mM VPA at 2 and 3 pdf. It was also demonstrated that 2 mM VPA exposure affected color preference of the zebrafish larvae, reducing blue color preference at 5 dpf larvae. The altered color preference was restored at 10 dpf larvae. These results suggest that VPA exposure may cause molecular, cellular, and behavioral alterations in early developmental stage of the zebrafish.

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Hypoxia stimulates neural stem cell proliferation by increasing HIF"‘1Î± expression and activating Wnt/Î²-catenin signaling

Cited by 62 publications

References 52 publications

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

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

Potential role of heat shock protein 90 in regulation of hyperthermia-driven differentiation of neural stem cells

Valproic Acid Decreases Cell Proliferation and Color Preference in the Zebrafish Larvae

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