ZMYND8 is a primary HIF coactivator that mediates breast cancer progression

Chen, Yan; Wang, Yingfei; Luo, Weibo

doi:10.1080/23723556.2018.1479619

Cited by 8 publications

(5 citation statements)

References 9 publications

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“…The prognostic effect of ZMYND8 expression was also con rmed in an independent cohort of TCGA dataset. Additionally, ZMYND8 is acetylated by the histone acetyltransferase p300 and promotes the HIF target gene expression (Chen et al 2018a). Interestingly, high expression of both HIF and p300 are associated with aggressive features and poor prognosis of HCC (Li et al 2011;Xiang et al 2012).…”

Section: Discussionmentioning

confidence: 99%

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Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma

Choi

Lee

Koh

et al. 2021

J Cancer Res Clin Oncol

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Background: ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8) has been known to play an important role in tumor regulation in various types of cancer. However, the results of ZMYND8 expression and their clinical signi cance in hepatocellular carcinoma (HCC) have not yet been published. In the present study, we investigate the expression of ZMYND8 protein and mRNA in HCC and elucidate its prognostic signi cance. Methods: ZMYND8 protein and mRNA expression in 283 and 234 HCCs were investigated using immunohistochemistry and quantitative real-time polymerase chain reactions. The relationships between ZMYND8 expression with clinicopathologic features and prognosis of HCC patients were evaluated. Furthermore, we performed the invasion, migration, apoptosis, soft agar formation assay and sphere formation assay in HCC cell lines, and evaluated tumorigenicity in a nude mouse model, after ZMYND8 knockdown.Results: Overexpression of ZMYND8 protein and mRNA was observed in 20.5% and 26.9% of HCC cases, respectively. High ZMYND8 expression showed signi cant correlations with microvascular invasion, high Edmondson grade, advanced American Joint Committee on Cancer (AJCC), and increased alpha-fetoprotein level. ZMYND8 mRNA overexpression was an independent prognostic factor for predicting early recurrence as well as short recurrence-free survival (RFS). Downregulation of ZMYND8 reduced migration and invasion of HCC cells, and promoted apoptosis of HCC cells in an in vitro model. In a xenograft nude mouse model, knockdown of ZMYND8 signi cantly reduced tumor growth.Conclusions: ZMYND8 mRNA overexpression could be a prognostic marker of shorter RFS in HCC patients after curative resection. ZMYND8 might play an important role in the proliferation and progression of HCC and could be a promising candidate for targeted therapy.

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Section: Discussionmentioning

confidence: 99%

“…(Chen and Lou 2017). Under a hypoxia state, ZMYND8 physically interacts with HIF-1a and HIF-2a, and activates HIF transcriptional activity in breast cancer(Chen et al 2018a;Chen et al 2018b).…”

mentioning

confidence: 99%

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma

Choi

Lee

Koh

et al. 2021

J Cancer Res Clin Oncol

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“…Research has uncovered ZMYND8 to be a tumor suppressor in human breast cancer, cervical cancer, and prostate cancer by retinoic acid mediation or functioning as a transcriptional corepressor 9,14. However, in recent years, reports appeared pointing to acetylation of ZMYND8 mediating progression and metastasis of breast cancer by interacting with HIF-dependent transcriptional program,24 and a ZMYND8 – RELA fusion gene was found to increase dramatically via the NFκB signal pathway in acute erythroid leukaemia 25. Copy numbers of ZMYND8 are also increased two- to threefold fold in several cancer cell lines according to the UK Institute of Cancer Research and Catalogue of Somatic Mutations in Cancer (COSMIC).…”

Section: Discussionmentioning

confidence: 99%

<p>Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma</p>

Chen¹,

Liu²,

Rothenberg³

et al. 2019

CMAR

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PurposeZMYND8 is closely correlated with cancerous proliferation and invasiveness. However, its prognostic value has not been estimated in a nasopharyngeal carcinoma (NPC). The purpose of this study was to elucidate the status of ZMYND8 expression and its prognostic significance in NPCs.MethodsThe status of ZMYND8 expression was investigated by immunohistochemistry for NPC samples in the study. The cutoff value of ZMYND8 expression was confirmed in NPCs using ROC-curve analysis. Correlations between ZMYND8 expression and clinicopathological variables and patient prognosis were analyzed by various statistical methods.ResultsOur study showed that low expression of ZMYND8 strongly correlated with late T stage in NPCs (P<0.05). Kaplan–Meier survival analysis revealed a significant association between low ZMYND8 expression and worse overall survival (P<0.05). Most importantly, Cox regression analysis confirmed ZMYND8 expression in NPC could be an independent prognostic factor.ConclusionLow expression of ZMYND8 could be of importance, due to its displaying more aggressive behavior in NPC. Therefore, ZMYND8 expression might serve as an independent prediction factor in patients with NPCs.

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“…Increased transcriptional activity of HIFs, both HIF-1α, and HIF-2α, leads to the upregulation of ZMYND8, closing the loop. ZMYND8 upregulation and a role in the progression and metastasis of breast cancer were reported to be associated with the activity of the hypoxia-inducible factors [ 29 ]. Extracellular ATP can also drive HIFs’ activation in normoxia via the Akt pathway [ 30 ].…”

Section: Activation Of the Hypoxia-inducible Factor In Cancersmentioning

confidence: 99%

The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy

Kozal

Krześlak

2022

Cancers

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Hypoxia is a common feature associated with many types of cancer. The activity of the hypoxia-inducible factors (HIFs), the critical element of response and adaptation to hypoxia, enhances cancer hallmarks such as suppression of the immune response, altered metabolism, angiogenesis, invasion, metastasis, and more. The HIF-1α and HIF-2α isoforms show similar regulation characteristics, although they are active in different types of hypoxia and can show different or even opposite effects. Breast cancers present several unique ways of non-canonical hypoxia-inducible factors activity induction, not limited to the hypoxia itself. This review summarizes different effects of HIFs activation in breast cancer, where areas such as metabolism, evasion of the immune response, cell survival and death, angiogenesis, invasion, metastasis, cancer stem cells, and hormone receptors status have been covered. The differences between HIF-1α and HIF-2α activity and their impacts are given special attention. The paper also discusses perspectives on using hypoxia-inducible factors as targets in anticancer therapy, given current knowledge acquired in molecular studies.

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ZMYND8 is a primary HIF coactivator that mediates breast cancer progression

Cited by 8 publications

References 9 publications

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma

Validation of ZMYND8 as a new treatment target in hepatocellular carcinoma

<p>Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma</p>

The Role of Hypoxia-Inducible Factor Isoforms in Breast Cancer and Perspectives on Their Inhibition in Therapy

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