Expression of myeloid zinc finger 1 and the correlation to clinical aspects of oral squamous cell carcinoma

Ko, Chung-Po; Yang, Li‐Chiu; Chen, Chih‐Jung; Yeh, Kun‐Tu; Lin, Shu-Hui; Yang, Shun‐Fa; Chen, Mu‐Kuan; Lin, Chiao‐Wen

doi:10.1007/s13277-015-3419-x

Cited by 9 publications

(13 citation statements)

References 27 publications

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“…Loss of nuclear expression of MZF1 has been associated with more advanced clinical stages in oral squamous cell carcinoma indicating that MZF1 can act as a negative regulator of tumorigenesis , while we observed both GABP and MZF1 have nuclear expression, and induce tumor growth through the activation of YAP1 in OS. Previous studies indicated that YAP1 may associate with promoters of genes which are important for the pluripotency of ESCs , through the mediation of the TEAD TF .…”

Section: Discussionmentioning

confidence: 53%

Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells

et al. 2017

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The transcription factor (TF) yes-associated protein 1 (YAP1) is a major effector of the tumor suppressive Hippo signaling pathway and is also necessary to maintain pluripotency in embryonic stem cells. Elevated levels of YAP1 expression antagonize the tumor suppressive effects of the Hippo pathway that normally represses YAP1 function. High YAP1 expression is observed in several types of human cancers and is particularly prominent in cancer stem cells (CSCs). The stem cell TF Sox2, which marks and maintains CSCs in osteosarcomas (OSs), promotes YAP1 expression by binding to an intronic enhancer element and YAP1 expression is also crucial for the maintainance of OS stem cells. To further understand the regulation of YAP1 expression in OSs, we subjected the YAP1 intronic enhancer to scanning mutagenesis to identify all DNA cis-elements critical for enhancer function. Through this approach, we identified two novel TFs, GA binding protein (GABP) and myeloid zinc finger 1 (MZF1), which are essential for basal YAP1 transcription. These factors are highly expressed in OSs and bind to distinct sites in the YAP1 enhancer. Depletion of either factor leads to drastically reduced YAP1 expression and thus a reversal of stem cell properties. We also found that YAP1 can regulate the expression of Sox2 by binding to two distinct DNA binding sites upstream and downstream of the Sox2 gene. Thus, Sox2 and YAP1 reinforce each others expression to maintain stemness and tumorigenicity in OSs, but the activity of MZF1 and GABP is essential for YAP1 transcription. Stem Cells 2017;35:2340-2350.

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Section: Discussionmentioning

confidence: 53%

Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells

et al. 2017

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“…24,27 In epidemiological studies, a reduced MZF1 expression in OSCC patients was associated with a larger tumour size and advanced clinical tumour stadium. 25 The observed tumour-specific expression patterns of MZF1 explain the cell line specific binding specificities: After the results of the TF array (data not shown), regarding the influence of CSE on MZF1 activity, the binding specificity after incubation with 10% CSE was examined. In this context, for both VEGF promoter reporter constructs, an elevated binding specificity of MZF1 was observed after CSE incubation in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

“…24 Interestingly, in patients with OSCC, a loss of MZF1 expression is associated with advanced stage and increased tumour size. 25 Therefore, we investigated the transcription factor MZF1 as a potential cigarette smoke regulated activator of VEGF-gene expression dependent on VEGF promoter polymorphism SNP 405.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke modulates binding of the transcription factor MZF1 to the VEGF promoter and regulates VEGF expression in dependence of genetic variation SNP 405

Krüger¹,

Metzger

Al‐Nawas³

et al. 2020

J Oral Pathology Medicine

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Background Vascular endothelial growth factor (VEGF) affects carcinogenesis of the upper aerodigestive tract. Cigarette smoke (CSE) influences VEGF‐gene regulation. The single nucleotide polymorphism +405 G/C (SNP +405 G/C) and the transcriptional factor (TF) myeloid zinc finger 1 (MZF1) are endogenic regulators of the VEGFpromoter as the polymorphism 405 potentially affects binding of the transcription factor MZF1. Therefore, this in vitro study analysed cancer cells of the upper aerodigestive tract after CSE incubation concerning MZF1‐binding specificity and VEGF expression in dependency of VEGF polymorphism +405 G/C compared to wild type (wt). Methods In human alveolar epithelial‐like type‐II cells (A549) and oral squamous cell cancer cells (HNSCCUM‐02T) SNP +405 G/C‐ and MZF1‐dependent VEGF promoter activity and VEGF expression were analysed by qRT‐PCR and Western blot after incubation with 10% CSE. Temporary knock‐down of MZF1 was performed using siRNA. MZF1 binding was analysed by Co‐Chromatin‐Immunoprecipitation (Co‐ChiP) (each test n = 3). Results We found a stronger MZF1 binding to VEGF polymorphism 405 in A549 cells (P < .05) compared to HNSCCUM‐02T cells (P = .02), where MZF1 binding was reduced. MZF1 knock out reduced VEGF promoter activity in HNSCCUM‐02T cells, showing the relevance of the factor for transcriptional activation of the VEGF promoter. Finally, we found that CSE increases promoter activity in both cell lines and no significant differences between the two analysed polymorphisms concerning their activating capacity. Conclusion In summary, both VEGF promoter polymorphisms are similar effective in terms of transcriptional activity, and MZF1 is a transcriptional activator of VEGF promoter. Moreover, cigarette smoke increases MZF1 binding of VEGF‐promoter and directly affects VEGF‐gene regulation.

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“…Ko et al reported_ that negative MZF1 expression predicted a significantly poor overall survival rate in oral squamous cell carcinoma (SCC) patients [12]. Several similar studies indicated that MZF1 could act as a tumour suppressor in prostate, cervical, breast and colon cancer and T-cell lymphoma [4, 6, 7, 14, 15].…”

Section: Discussionmentioning

confidence: 99%

“…Further studies demonstrated the critical function of MZF1 as a potential prognostic biomarker for oral squamous cell carcinoma [12]. Recently, Lee J H et al revealed that MZF1 is a putative transcription factor that directly binds to the core region of the SMAD4 promoter and stimulates transcriptional activity to play a role in inhibiting gastric cancer [13].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Myeloid Zinc Finger 1 Expression in the Progression of Gastric Tumourigenesis

Yang

et al. 2017

Cell Physiol Biochem

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Background/Aims: To investigate the clinical significance of myeloid zinc finger 1 (MZF1) expression in various gastric mucosal lesions including chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS) and gastric cancer (GC) in comparison with normal tissues and gastric cell lines. Methods: MZF1 protein expression was detected using immunohistochemical staining in 37 CSG, 88 CAG, 77 IM, 51 DYS, 165 GC and 8 normal tissue samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect the level of MZF1 in gastric cell lines, 15 normal tissues and 34 GC samples, as well as 2 groups of paired primary GC and adjacent normal samples. Results: Reduced MZF1 expression was detected in most GC cells and tissues. Among the gastric tissues consisting of various stages of lesions (normal, CSG, CAG, IM, DYS and GC), MZF1 protein expression was downregulated in precancerous lesions and GC. The data from clinical analyses showed that decreased MZF1 expression was correlated with tumour invasion (p = 0.044), lymph node metastasis (p = 0.048) and poor prognosis of GC patients (p = 0.003). Moreover, MZF1 was identified as an independent prognostic biomarker for GC patients in multivariate Cox regression analysis (p = 0.009). Conclusion: Downregulation of MZF1 was associated with gastric tumourigenesis, which may be a novel early predictive and prognostic biomarker in GC patients.

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Expression of myeloid zinc finger 1 and the correlation to clinical aspects of oral squamous cell carcinoma

Cited by 9 publications

References 27 publications

Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells

Myeloid Zinc Finger 1 and GA Binding Protein Co-Operate with Sox2 in Regulating the Expression of Yes-Associated Protein 1 in Cancer Cells

Cigarette smoke modulates binding of the transcription factor MZF1 to the VEGF promoter and regulates VEGF expression in dependence of genetic variation SNP 405

Clinical Significance of Myeloid Zinc Finger 1 Expression in the Progression of Gastric Tumourigenesis

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