Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cai, Junyan; Xu, Tongtong; Wang, Ye; Chang, Jing-Jian; Li, Jian; Chen, Xiaoyang; Chen, Xi; Yin, Yifei; Ni, Xuejun

doi:10.3892/ijo.2018.4564

Cited by 31 publications

(35 citation statements)

References 42 publications

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“…When HDAC4 was overexpressed in U251 cells, the glioma cell's invasive ability was enhanced. By inhibiting the expression of HDAC4 in U251 cells, the invasive ability was diminished [7]. These findings from previous research support the use of HDAC4 as a therapeutic target for glioma, as inhibition of this enzyme would result in decreased proliferation and invasiveness of this tumor type.…”

Section: Hybrid Compoundssupporting

confidence: 69%

“…It has been shown that increased levels of HDAC4 decrease HDAC4, which is elevated in glioma cells, has been demonstrated to be essential for tumorigenesis of glioma. When HDAC4 was knocked down in U251, a human gliomablastoma cell line, the proliferation ability of the cells was significantly decreased [7]. When HDAC4 was overexpressed in U251 cells, the glioma cell's invasive ability was enhanced.…”

Section: Hybrid Compoundsmentioning

confidence: 99%

“…Glioma, the most deadly brain tumor has recently been shown to overexpress histone deacetylase 4 (HDAC4). The upregulation of HDAC4 in glioma cells supports tumorigenesis [7]. Thus, inhibition of HDAC4 may present an option to develop a targeted therapeutic for glioma.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

In silico Design of Novel Histone Deacetylase 4 Inhibitors: Design Guidelines for Improved Binding Affinity

Stoddard

Dodson

Adams

et al. 2019

IJMS

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Histone deacetylases (HDAC) are being targeted for a number of diseases such as cancer, inflammatory disease, and neurological disorders. Within this family of 18 isozymes, HDAC4 is a prime target for glioma, one of the most aggressive brain tumors reported. Thus, the development of HDAC4 inhibitors could present a novel therapeutic route for glioma. In this work, molecular docking studies on cyclopropane hydroxamic acid derivatives identified five novel molecular interactions to the HDAC4 receptor that could be harnessed to enhance inhibitor binding. Thus, design guidelines for the optimization of potent HDAC4 inhibitors were developed which can be utilized to further the development of HDAC4 inhibitors. Using the developed guidelines, eleven novel cyclopropane hydroxamic acid derivatives were designed that outcompeted all original cyclopropane hydroxamic acids HDAC4 inhibitors studied in silico. The results of this work will be an asset to paving the way for further design and optimization of novel potent HDAC4 inhibitors for gliomas.

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Section: Hybrid Compoundssupporting

confidence: 69%

Section: Hybrid Compoundsmentioning

confidence: 99%

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In silico Design of Novel Histone Deacetylase 4 Inhibitors: Design Guidelines for Improved Binding Affinity

Stoddard

Dodson

Adams

et al. 2019

IJMS

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“…14 Kang et al purported that HDAC4 accelerated cell progression of gastric cancer via inhibiting p21 15 and Cai et al found the oncogenic role of HDAC4 in glioma. 16 Also, HDAC4 has been testified to enhance OS cell proliferation and invasion, 17 but its association with miR-432-5p and circCRIM1 is unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>Knockdown of CircCRIM1 Inhibits HDAC4 to Impede Osteosarcoma Proliferation, Migration, and Invasion and Facilitate Autophagy by Targeting miR-432-5p</p>

Li¹,

Feng²,

Li³

et al. 2020

CMAR

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Background: Circular RNAs (circRNAs) serve for a genre of considerable modulatory molecules that have been largely researched in human cancers. However, the contribution of circRNA cysteine-rich transmembrane bone morphogenetic protein regulator 1 (circCRIM1) to osteosarcoma (OS) is completely unclear. Methods: All the RNA levels were examined via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular proliferation and migration/invasion were, respectively, analyzed using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay and transwell assay. The determination of all protein expression was administrated by Western blot. Dual-luciferase reporter assay was used for proving the target combination. The exploration of circCRIM1 in vivo was performed by xenograft assay. Results: In OS tissues and cells, circCRIM1 was differentially up-regulated. Functionally, cell proliferation, migration and invasion were suppressed while autophagy was promoted after circCRIM1 was down-regulated in OS cells. Mechanistically, mircoRNA-432-5p (miR-432-5p) was a miRNA target of circCRIM1 and the inhibitory effect of circCRIM1 knockdown on OS progression was achieved by targeting miR-432-5p. Moreover, histone deacetylase 4 (HDAC4) was a downstream gene of miR-432-5p and circCRIM1 targeted miR-432-5p to upregulate HDAC4 level. MiR-432-5p inhibited proliferation, migration, and invasion but enhanced autophagy of OS cells through down-regulating HDAC4. In vivo, knockdown of circCRIM1 decreased OS growth via acting on the miR-432-5p/HDAC4 axis. Conclusion: Our findings elucidated the oncogenic function of circCRIM1 in OS via the regulation of the miR-432-5p/HDAC4 axis, affording a novel view about how circRNA participated in OS development.

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“…The expression of HDAC4 and HDAC5 was downregulated in high-grade gliomas when compared with low-grade ones, and was associated with a favorable clinical outcome [17,18]. Interestingly, HDAC4 and HDAC5 have been reported to act as oncogenes by promoting the proliferation of glioma cells, as well as their invasive ability [19,20]. KAT2A, also known as GCN5, functions primarily as a transcriptional activator, although it also represses NF-κB signaling by promoting the ubiquitination of the NF-κB subunit RELA [21].…”

Section: Discussionmentioning

confidence: 99%

Multi-omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma

et al. 2020

Preprint

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Background: Lysine acetylation is a crucial kind of protein modification and is related to the malignant development of various cancers. But their roles in glioma are still unclear and needed concluded comprehensively. Methods: In this study, we comprehensively analyzed the expression levels of 33 lysine acetylation regulators (LARs) and prognostic roles by using public data, including the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The prognostic roles of LARs were judged by univariate Cox regression. Consensus clustering was applied to result in three stratified glioma subtypes (LA1, 2, and 3) with different clinical outcomes. We also constructed a risk signature for predicting the overall survival of glioma patients by using least absolute shrinkage and selection operator regression (LASSO regression). Besides, copy number variations (CNVs) and single nucleotide polymorphism (SNP) of LARs were also analyzed in our study. Results: We found the mRNA expression levels of most of LARs were dysregulated in gliomas and associated with the prognosis of glioma patients. The risk signature constructed by 14 LARs presented an independent prognostic role in both the CGGA (HR:1.96, 95%CI:1.33-2.90) and TCGA (HR:1.48, 95%CI:1.08-2.03) datasets and robust predictive effects in the ROC curves with all of area under curves more than 0.800. Moreover, the copy number variations of LARs were also significantly related to the prognosis of glioma patients, in which HDAC1 (1p) was one of the oncogenes lost in 1p/19q codeletion events, while SIRT2 (19q) and EP300 (22q) may act as tumor suppressors in gliomas with 19q or 22q deletions, respectively. Conclusion: LARs are potential biomarkers for the malignant progression of gliomas, and our results could be useful for predicting the OS of glioma patients and provide some clues in searching the functions of LARs in glioma progression. Keywords: glioma, lysine acetylation regulator, epigenetic, prognostic signature, biomarker.

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Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cited by 31 publications

References 42 publications

In silico Design of Novel Histone Deacetylase 4 Inhibitors: Design Guidelines for Improved Binding Affinity

In silico Design of Novel Histone Deacetylase 4 Inhibitors: Design Guidelines for Improved Binding Affinity

<p>Knockdown of CircCRIM1 Inhibits HDAC4 to Impede Osteosarcoma Proliferation, Migration, and Invasion and Facilitate Autophagy by Targeting miR-432-5p</p>

Multi-omics Prognostic Analysis of Lysine Acetylation Regulators in Glioma

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