Histone deacetylase 5 promotes the proliferation of glioma cells by upregulation of Notch 1

Liu, Quan; Zheng, Jiemin; Chen, Jia‐Kang; Yan, Xianlei; Chen, Hongmou; Nong, Weixia; Huang, Heqing

doi:10.3892/mmr.2014.2395

Cited by 37 publications

(41 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies had shown that the expression of HDAC5 was increased in human glioma tissues and U87 and LN‐229 cell lines. In addition, overexpression of HDAC5 promoted proliferation of glioma cells . In this study, Hutt et al .…”

Section: Expression Of Hdacs In Cancersmentioning

confidence: 50%

Histone deacetylases function as novel potential therapeutic targets for cancer

Zhang

Shang

Chen

et al. 2016

Hepatology Research

View full text Add to dashboard Cite

Diverse cellular functions, including tumor suppressor gene expression, DNA repair, cell proliferation and apoptosis, are regulated by histone acetylation and deacetylation. Histone deacetylases (HDACs) are enzymes involved in remodeling of chromatin by deacetylating the lysine residues. They play a pivotal role in epigenetic regulation of gene expression. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation have been implicated in the pathogenesis of various diseases, including cancer. Histone deacetylases have become a target for the development of drugs for treating cancer because of their major contribution to oncogenic cell transformation. Overexpression of HDACs correlates with tumorigenesis. Previous work showed that inhibition of HDACs results in apoptosis and the inhibition of cell proliferation in multiple cells. A significant number of HDAC inhibitors have been developed in the past decade. These inhibitors have strong anticancer effects in vitro and in vivo, inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. In addition, HDAC-mediated deacetylation alters the transcriptional activity of nuclear transcription factors, including p53, E2F, c-Myc, and nuclear factor-κB, as well as the extracellular signal-regulated kinase1/2, phosphatidylinositol 3-kinase, Notch, and Wnt signaling pathways. This review highlights the role of HDACs in cancer pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.

show abstract

Section: Expression Of Hdacs In Cancersmentioning

confidence: 50%

Histone deacetylases function as novel potential therapeutic targets for cancer

Zhang

Shang

Chen

et al. 2016

Hepatology Research

View full text Add to dashboard Cite

show abstract

“…In the gbmSYGNAL network, both romidepsin and miR-486-3p target HDAC5, which is up-regulated in GBM patient tumors and known to increase proliferation of GBM cells (Liu et al, 2014). Therefore, we hypothesized that the potentially synergistic effect of romidepsin and miR-486-3p on HDAC5 would generate a stronger and longer-lasting treatment.…”

Section: Resultsmentioning

confidence: 99%

Causal Mechanistic Regulatory Network for Glioblastoma Deciphered Using Systems Genetics Network Analysis

et al. 2016

View full text Add to dashboard Cite

Summary We developed the transcription factor (TF)-target gene database and the SYstems Genetics Network AnaLysis (SYGNAL) pipeline to decipher transcriptional regulatory networks from multi-omic and clinical patient data, and applied these tools to 422 patients with glioblastoma multiforme (GBM). The resulting gbmSYGNAL network predicted 112 somatically mutated genes or pathways that act through 74 TFs and 37 miRNAs (67 not previously associated with GBM) to dysregulate 237 distinct co-regulated gene modules associated with patient survival or oncogenic processes. The regulatory predictions were associated to cancer phenotypes using CRISPR-Cas9 and small-RNA perturbation studies, and also demonstrated GBM specificity. Two pairwise combinations (ETV6–NFKB1 and romidepsin–miR-486-3p) predicted by the gbmSYGNAL network had synergistic anti-proliferative effects. Finally, the network revealed that mutations in NF1 and PIK3CA modulate IRF1-mediated regulation of MHC class I antigen processing and presentation genes to increase tumor lymphocyte infiltration and worsen prognosis. Importantly, SYGNAL is widely applicable for integrating genomic and transcriptomic measurements from other human cohorts.

show abstract

“…Growing evidence has revealed that HDAC4 was frequently dysregulated in human malignancies (12)(13)(14)(15). HDAC5 are increased in human glioma tissues and promoted the proliferation of glioma cells by the upregulation of Notch 1 (33). However, the involvement of HDAC4 in gliomagenesis, migration and invasiveness remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cai

Wang

et al. 2018

Int J Oncol

View full text Add to dashboard Cite

Glioma is the most lethal type of primary brain tumor characterized by aggressiveness and a poor prognosis. Histone deacetylase 4 (HDAC4) is frequently dysregulated in human malignancies. However, its biological functions in the development of glioma are not fully understood. The present study aimed to evaluate HDAC4 expression in human glioma and to elucidate the mechanistic role of HDAC4 in glioma. The results suggested that HDAC4 was significantly upregulated in glioma tissues and a number of glioma cell lines compared with adjacent non-tumor tissues and the non-cancerous human glial cell line SVG p12, respectively (P<0.05). The proliferation, adenosine triphosphate (ATP) levels and invasion ability were substantially enhanced in U251 cells with HDAC4 overexpression, and suppressed in U251 cells with a knockdown of HDAC4 compared with that in U251 cells transfected with the negative control. Knockdown of HDAC4 resulted in cell cycle arrest at the G0/G1 phase and induced the increase of reactive oxygen species level in U251 cells. Furthermore, HDAC4 overexpression was revealed to substantially inhibit the expression of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and the expression of E-cadherin and β-catenin in glioma U251 cells. Knockdown of HDAC4 substantially promoted the expression of CDK1 and CDK2 and vimentin in glioma U251 cells. Mechanistically, the results of the present study demonstrated that HDAC4 displayed a significant upregulation in glioma, and promoted glioma cell proliferation and invasion mediated through the repression of p21, p27, E-cadherin and β-catenin, and the potentiation of CDK1, CDK2 and vimentin. Altogether, the present study revealed that HDAC4 overexpression was central for the tumorigenesis of glioma, which may serve as a useful prognostic biomarker and potential therapeutic target for glioma.

show abstract

Histone deacetylase 5 promotes the proliferation of glioma cells by upregulation of Notch 1

Cited by 37 publications

References 21 publications

Histone deacetylases function as novel potential therapeutic targets for cancer

Histone deacetylases function as novel potential therapeutic targets for cancer

Causal Mechanistic Regulatory Network for Glioblastoma Deciphered Using Systems Genetics Network Analysis

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Contact Info

Product

Resources

About