The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis

Yu, Yanhui; Cao, Fengjun; Yu, Xuanji; Zhou, Ping; Di, Quanshu; Lei, Jian; Tai, Yan; Wu, Huifeng; Li, X.; Wang, X.; Zhang, W.; Li, P.; Li, Y.

doi:10.1007/s12094-017-1639-9

Cited by 28 publications

(35 citation statements)

References 28 publications

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“…Moreover, our results indicated that HDAC7 is necessary and sufficient to maintain the CSC phenotype in these cells [1]. Independently, studies from several laboratories showed that HDAC7 expression correlates with poor patient outcome, drug resistance, and metastasis in ovarian, gastric, lung, colon, and salivary cancers [19][20][21][22][23][24]. Interestingly, HDAC7 is the only HDAC family member that is degraded by all HDAC inhibitors tested, suggesting that it may be a point of convergence of HDAC inhibition [1,27,28,38].…”

Section: Activation Of Transcription By Hdacsmentioning

confidence: 56%

“…At least in the case of breast CSCs HDAC7 seems to play a critical role in regulating a differentiation program involving many oncogenes and stem cell transcription factors. It is possible that other HDACs may play a similar role in other tissue types, also HDAC7 may be involved in other tumors, as suggested by recent studies in ovarian, gastric, lung, colon, and salivary cancers [19][20][21][22][23][24].…”

Section: Discussionmentioning

confidence: 94%

“…While HDAC1 has been studied in many cancer types before [19][20][21], the role of HDAC7 has been emerging more recently. Since we first reported a specific role for HDAC7 in regulating CSCs, several papers showing that HDAC7 correlates with poor patient outcome, drug resistance, and metastasis in ovarian cancer and gastric cancer have been published [22,23]. Recently, it was shown that HDAC7 also promotes lung, colorectal cancer, and salivary tumorigenesis [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells

et al. 2019

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Chromatin regulation through histone modifications plays an essential role in coordinated expression of multiple genes. Alterations in chromatin induced by histone modifiers and readers regulate critical transcriptional programs involved in both normal development and tumor differentiation. Recently, we identified that histone deacetylases HDAC1 and HDAC7 are necessary to maintain cancer stem cells (CSCs) in both breast and ovarian tumors. Here, we sought to investigate the CSCspecific function of HDAC1 and HDAC7 mechanistically by using a stem-like breast cancer (BrCa) cell model BPLER and matched nonstem tumor cell (nsTC)-like HMLER, along with conventional BrCa cell lines with different CSC enrichment levels. We found that HDAC1 and HDAC3 inhibition or knockdown results in HDAC7 downregulation, which is associated with a decrease in histone 3 lysine 27 acetylation (H3K27ac) at transcription start sites (TSS) and super-enhancers (SEs) prominently in stem-like BrCa cells. Importantly, these changes in chromatin landscape also correlate with the repression of many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA, and XBP1. In stem-like BrCa cells, HDAC7 binds near TSS and to SEs of these oncogenes where it appears to contribute to both H3K27ac and transcriptional regulation. These results suggest that HDAC7 inactivation, directly or through inhibition of HDAC1 and HDAC3, can result in the inhibition of the CSC phenotype by downregulating multiple SE-associated oncogenes. The CSC selective nature of this mechanism and the prospect of inhibiting multiple oncogenes simultaneously makes development of HDAC7 specific inhibitors a compelling objective.

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Section: Activation Of Transcription By Hdacsmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells

et al. 2019

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“…Moreover, Peixoto P et al found that inhibiting HDAC7 reduced the tumorigenic activity of human glioblastoma and provided a new opportunity for tumor treatment [27]. Yu Y et al have shown that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer [28]. However, the Fig.…”

Section: Discussionmentioning

confidence: 99%

MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway

Zhang

Yuan

et al. 2020

World J Surg Onc

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Background: Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC). The purpose of this study was to explore the biological functions and potential mechanism of miR-489 in GC progression. Methods: Quantitative real-time PCR (qRT-PCR) and western blot were performed to examine the mRNA expression and protein levels of miR-489 and HDAC7. The relationship between miR-489 and HDAC7 was analyzed by Spearman rank correlation. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays were conducted for determining the effect of miR-489 and HDAC7 on GC cell viability, migration, and invasion. TargetScan and luciferase reporter assay were used to confirm the target gene of miR-489 in GC cells. Results: The findings showed that miR-489 was dramatically decreased in GC tissues and GC cell lines (SGC-7901 and MKN45). Moreover, it was closely correlated with overall survival (OS) and progression-free survival (PFS) of GC patients. Downregulation of miR-489 significantly promoted GC cell proliferation, invasion, and migration. Additionally, HDAC7 was confirmed as the direct target of miR-489. Knockdown of HDAC7 exerted inhibited effect on GC progression and it markedly overturned miR-489 inhibitor-medicated effect on GC cells. More interestingly, via targeting HDAC7, miR-489 blocked the activation of PI3K/AKT pathway in GC cells. Conclusions: Correctively, miR-489 played as a tumor suppressor in GC cell growth by targeting HDAC7, and miR-489 might function as a novel biomarker for diagnosis or therapeutic targets of human GC.

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“…HDAC7 regulates cell proliferation, differentiation, apoptosis, migration, and stemness in the physiological and pathological condition 12 . Aberrant expression of HDAC7 has been observed in the lung 13,14 , gastric 15 , breast 16,17 , and ovarian cancer 17 , glioma 18 , and hemolymphatic tumors 19,20 . High HDAC7 expression is correlated with metastasis and poor prognosis 13,15,20 .…”

Section: Introductionmentioning

confidence: 99%

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis

Xiao

Zhu

et al. 2020

Cell Death Dis

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HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.

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The expression of HDAC7 in cancerous gastric tissues is positively associated with distant metastasis and poor patient prognosis

Abstract: These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer.

Cited by 28 publications

References 28 publications

HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells

HDAC7 regulates histone 3 lysine 27 acetylation and transcriptional activity at super-enhancer-associated genes in breast cancer stem cells

MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis

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