Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

Zeng, Li; Yang, Xian; Wen, Yangping; Shi, Juan; Wang, Meng He; Zhang, Mei Yin; Zheng, Xiaohui; Wang, Hui Yun

doi:10.18632/aging.100980

Cited by 71 publications

(83 citation statements)

References 39 publications

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“…Disruption of the HDAC4-RelB-p52 complex by a HDAC4-mimetic polypeptide blocks the growth of multiple myeloma (16). Zeng et al (17) demonstrated that HDAC4 was overexpressed in esophageal squamous cell carcinoma, and HDAC4 overexpression was associated with an advanced clinical stage and poor survival. HDAC4 inhibition sensitized lung cancer A549 cells to doxorubicin resistance by reducing the phosphorylation of signal transducers and activators of transcription-1 (STAT1) and the expression of epidermal growth factor receptor (EGFR), which suggested an interaction between HDAC4, STAT1 and EGFR (18).…”

Section: Histone Deacetylase Hdac4 Promotes the Proliferation And Invmentioning

confidence: 99%

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cai

Wang

et al. 2018

Int J Oncol

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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.

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Section: Histone Deacetylase Hdac4 Promotes the Proliferation And Invmentioning

confidence: 99%

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Cai

Wang

et al. 2018

Int J Oncol

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“…Histone deacetylase 4 (HDAC4) plays global roles in the regulation of gene transcription, cell growth, survival and proliferation, and their aberrant expressions or activities contribute to cancer development . Zeng LS revealed that upregulated HDAC4 is associated with higher tumor grade, advanced clinical stage, and poor survival rate in esophageal carcinoma, also they found that HDAC4 promoted proliferation and G1/S cell cycle progression in EC cells . Vallabhapurapu SD demonstrated that HDAC4 and its downstream complex maintained repressive chromatin around pro‐apoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth .…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10] Zeng LS revealed that upregulated HDAC4 is associated with higher tumor grade, advanced clinical stage, and poor survival rate in esophageal carcinoma, also they found that HDAC4 promoted proliferation and G1/S cell cycle progression in EC cells. 11 Vallabhapurapu | 4585 SUN aNd QIN SD demonstrated that HDAC4 and its downstream complex maintained repressive chromatin around pro-apoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth. 12 Marroncelli N reported that HDAC4 regulated satellite cell proliferation and differentiation by targeting P21 and Sharp1 genes.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

Sun

Qin

2018

Cancer Medicine

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Noncoding RNAs regulate the initiation and progression of osteosarcoma (OS). The role of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) playing in OS and whether the function it working out was achieved through HDAC4 pathway remain uncovered. In this study, we illustrated that MALAT1 was upregulated and was correlated with poor prognosis in OS patients. Meanwhile, we demonstrated that a depression of MALAT1 suppressed proliferation and promoted apoptosis in OS cell line HOS and 143B. Further, we verified that MALAT1 exerting its function via upregulating of histone deacetylase 4 (HDAC4). Through an online prediction, a series of luciferase assays and RNA pull‐down assays, we demonstrated that both MALAT1 and HDAC4 were the targets of microRNA‐140‐5p (miR‐140‐5p) via sharing a similar microRNA responding elements. Even further, we revealed that MALAT1 served as a ceRNA of HDAC4 via decoying of miR‐140‐5p. Finally, we proved that MALAT1 promoted OS tumor growth in an in vivo animal study. In summary, the outcomes of this study demonstrated the complex ceRNA network among MALAT, miR‐140‐5p, and HDAC4‐mediated proliferation and apoptosis in OS. This study might provide a new axial in molecular treatment of OS.

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“…This can likely be explained by the inability of the TNM staging system to accurately predict the prognosis of patients with resectable ESCC [7]. Some patients with early-stage ESCC rapidly develop local and regional recurrences and distant metastases after esophagectomy [8]. Therefore, it is imperative to identify novel prognostic biomarkers to assist oncologists in improving the predictive accuracy of the TNM staging system for ESCC.…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of LINC01133 for Unfavorable Prognosis was Impacted by Alcohol in Esophageal Squamous Cell Carcinoma

Yang

Tien

et al. 2018

Cell Physiol Biochem

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Background/Aims: Considerable evidence indicates that long noncoding RNAs (lncRNAs) exert importantly regulatory functions during human cancer initiation and progression and are promising biotargets in the flight against cancer. Methods: In this study, we evaluated the role of the lncRNA LINC01133 in esophageal squamous cell carcinoma (ESCC). LINC01133 expression in ESCC was examined by quantitative real-time PCR. The correlations between LINC01133 expression and clinicopathological variables and survival were examined by the χ² test, Kaplan–Meier method, log-rank test, and univariate Cox regression analysis. Results: LINC01133 expression levels were frequently lower in ESCC tissues and cell lines than in paired normal tissues and an immortalized esophageal epithelial cell line, respectively. The expression of LINC01133 decreased in a TNM stage- and lifestyle-independent manner. LINC01133 was an independent protective factor and had an anti-tumor effect in the early stage of ESCC development. More importantly, we discovered that drinking status in our cohort impaired the predictive accuracy of LINC01133 for patients with ESCC. Furthermore, a new risk model combining LINC01133 expression, drinking status, and TNM stage provided better survival discrimination compared with three other predictors. Conclusions: Our data indicate that a loss of LINC01133 expression is a potential poor prognostic biomarker and therapeutic target for ESCC and provide additional prognostic information to improve the outcomes of ESCC patients.

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Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

Cited by 71 publications

References 39 publications

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Histone deacetylase HDAC4 promotes the proliferation and invasion of glioma cells

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

Predictive Value of LINC01133 for Unfavorable Prognosis was Impacted by Alcohol in Esophageal Squamous Cell Carcinoma

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