The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells

Jia, Di; Huang, Lan; Bischoff, Joyce; Moses, Marsha A.

doi:10.1096/fj.14-258947

Cited by 19 publications

(17 citation statements)

References 62 publications

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“…7397-EB-050, Waltham, MA) or 100 nM EphB4 inhibitor 19 (Sigma, NVP BHG 712, St. Louis, MO) were added to the lower chamber to act as a chemoattractant. After 24 h, cells remaining in the upper chamber were aspirated; cells in the bottom chamber were fixed, permeabilized, and stained using Diff-Quik Stain Set (Siemens, Malvern, PA) as previously published 20,21 . Invasion assays were performed in a similar fashion as above using Matrigel invasion chambers (Thermo Fisher Scientific, Waltham, MA).…”

Section: Migration and Invasion Assaysmentioning

confidence: 99%

Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients

et al. 2020

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We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2: EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n = 30), other cerebrovascular disease (n = 14) and control patients (n = 29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p = 0.04) and migration (p = 0.08), impaired tube formation (p = 0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p = 0.03 and p < 0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2 > 25.7 pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Posttreatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.

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Section: Migration and Invasion Assaysmentioning

confidence: 99%

Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients

et al. 2020

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“…Jia et al 46 verified that the deletion of the gene that encodes this protein in primary microvascular endothelial cells significantly decreases migration and tumor invasion by reducing the levels of MMP-2 and impairing the signaling of VEGF receptor 2. However, the authors did not observe effects of ZNF24 on the regulators of MMP-2 activity or its tissue inhibitors.…”

mentioning

confidence: 99%

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

Holanda

Oliveira²,

Cruz³

et al. 2017

Rev. Assoc. Med. Bras.

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Zinc is the catalytic component of proteins that regulate responses to DNA damage, intracellular signaling enzymes, and matrix metalloproteinases, which are important proteins in carcinogenesis. The objective of this review is to bring current information on the participation of zinc and matrix metalloproteinases types 2 and 9 in mechanisms involved in the pathogenesis of breast cancer. We conducted a literature review, in consultation with the PubMed, Lilacs, and Scielo databases. The zinc and cysteine residues are structural elements shared by all members of the family of matrix metalloproteinases, and these proteins appear to be involved in the propagation of various types of neoplasms, including breast cancer. Moreover, transported zinc is likely to be used for the metalation of the catalytic domain of the newly synthesized metalloproteinases before the latter are secreted. Accordingly, increase in zinc concentrations in cellular compartments and the reduction of this trace element in the blood of patients with breast cancer appear to alter the activity of metalloproteinases 2 and 9, contributing to the occurrence of malignancy. Thus, it is necessary to carry out further studies with a view to clarify the role of zinc and metalloproteinases 2 and 9 in the pathogenesis of breast cancer.

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“…Besides, DeepHistone recovers SREBF2, HOXA5 and ZNF24 in human umbilical vein endothelial primary (HUVEC) cell line (E122) and NKX6-1 in embryonic stem cell line (E008). Those recovered transcription factors are verified to play an important role in the corresponding cell line [44][45][46][47][48]. To sum up, DeepHistone has the ability to recover potential functional transcription factor corresponding to specific cell line.…”

Section: Deephistone Recovers Tf Binding Motifsmentioning

confidence: 99%

DeepHistone: a deep learning approach to predicting histone modifications

Yin¹,

Wu²,

Lv³

et al. 2018

EasyChair Preprints

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Motivation: Quantitative detection of histone modifications has emerged in the recent years in a major means for understanding such biological processes as chromosome packaging, transcriptional activation, and DNA damage. However, high-throughput experimental techniques such as ChIP-seq are usually expensive and time-consuming, prohibiting the establishment of a histone modification landscape for hundreds of cell types across dozens of histone markers. These disadvantages have been appealing for computational methods to complement experimental approaches towards large-scale analysis of histone modifications. Results: We proposed a deep learning framework to integrate sequence information and chromatin accessibility data for the accurate prediction of modification sites specific to different histone markers. Our method, named DeepHistone, outperformed several baseline methods in a series of comprehensive validation experiments, not only within an epigenome but also across epigenomes. Besides, sequence signatures automatically extracted by our method was consistent with known transcription factor binding sites, thereby giving insights into regulatory signatures of histone modifications. As an application, our method was shown to be able to distinguish functional single nucleotide polymorphisms from their nearby genetic variants, thereby having the potential to be used for exploring functional implications of putative disease-associated genetic variants. Conclusions: DeepHistone demonstrated the possibility of using a deep learning framework to integrate DNA sequence and experimental data for predicting epigenomic signals. With the state-of-the-art performance, DeepHistone was expected to shed light on a variety of epigenomic studies.

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The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells

Cited by 19 publications

References 62 publications

Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients

Dysregulation of the EphrinB2−EphB4 ratio in pediatric cerebral arteriovenous malformations is associated with endothelial cell dysfunction in vitro and functions as a novel noninvasive biomarker in patients

Zinc and metalloproteinases 2 and 9: What is their relation with breast cancer?

DeepHistone: a deep learning approach to predicting histone modifications

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