ZNF750 inhibits the proliferation and invasion of melanoma cells through modulating the Wnt/b-catenin signaling pathway

Du, Yong; Lv, Guozhong; Jing, Changrui; Liu, Junjie; Liu, Jing

doi:10.5603/fhc.a2020.0026

Cited by 6 publications

(7 citation statements)

References 32 publications

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“…GRLH3 is a member of the grainyhead family of transcription factors and a low expression of this protein has been described in nonmelanoma skin tumors [17]. Another relevant gene in Molecular 1 group is ZNF750: its overexpression decreases proliferation of melanoma cells, whereas its depletion causes opposite effects [18].Molecular 1 comprised most of primary tumors included in the TCGA and GEM cohorts. The group showed higher activity of the nodes "epidermis development" and "keratin".…”

Section: Discussionmentioning

confidence: 99%

Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma

Trilla-Fuertes

Gámez‐Pozo

Prado-Vázquez

et al. 2023

IJMS

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Immunotherapy based on anti-PD1 antibodies has improved the outcome of advanced melanoma. However, prediction of response to immunotherapy remains an unmet need in the field. Tumor PD-L1 expression, mutational burden, gene profiles and microbiome profiles have been proposed as potential markers but are not used in clinical practice. Probabilistic graphical models and classificatory algorithms were used to classify melanoma tumor samples from a TCGA cohort. A cohort of patients with advanced melanoma treated with PD-1 inhibitors was also analyzed. We established that gene expression data can be grouped in two different layers of information: immune and molecular. In the TCGA, the molecular classification provided information on processes such as epidermis development and keratinization, melanogenesis, and extracellular space and membrane. The immune layer classification was able to distinguish between responders and non-responders to immunotherapy in an independent series of patients with advanced melanoma treated with PD-1 inhibitors. We established that the immune information is independent than molecular features of the tumors in melanoma TCGA cohort, and an immune classification of these tumors was established. This immune classification was capable to determine what patients are going to respond to immunotherapy in a new cohort of patients with advanced melanoma treated with PD-1 inhibitors Therefore, this immune signature could be useful to the clinicians to identify those patients who will respond to immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma

Trilla-Fuertes

Gámez‐Pozo

Prado-Vázquez

et al. 2023

IJMS

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“…3A), DQF-COSY and E-COSY experiments, together with natural abundance 13 C-HSQC (Fig. 3B) and 15 N-sofast HMQC (Fig. 3C) spectra.…”

Section: Z* Has a Typical Znf Bba Foldmentioning

confidence: 99%

“…Both samples had a measured pH of 5.9. The experiments recorded on the H2O sample included 70 ms mixing time TOCSY (mlevgpphw5), 200 ms mixing time NOESY (noesygpphw5), and a natural abundance 15 Nsofast-HMQC (sfhmqcf3gpph). The names in parentheses are the Bruker pulse programs for the experiments.…”

Section: Nmr Spectroscopymentioning

confidence: 99%

“…Over the last few years it has become evident that in addition to skin differentiation ZNF750 has roles in oral (13) and esophageal (14) squamous cell carcinoma, melanoma (15), ocular sebaceous carcinoma (16), prostate (17) and breast cancers (18)(19)(20). A common mechanistic theme linking the involvement of ZNF750 in pathologies as varied as skin disease and cancers is that the transcription factor regulates cell differentiation.…”

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confidence: 99%

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NMR structure verifies the eponymous degenerate zinc finger domain of transcription factor ZNF750

Rua¹,

Whitehead²,

Alexandrescu³

2023

Preprint

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ZNF750 is a nuclear transcription factor that activates skin differentiation and has tumor suppressor roles in several cancers. Unusually, ZNF750 has only a single zinc-finger (ZNF) domain, Z*, with an amino acid sequence that differs markedly from the CCHH family consensus. Because of its sequence differences Z* is classified as degenerate, presumed to have lost the ability to bind the zinc ion required for folding. AlphaFold predicts an irregular structure for Z* with low confidence. Low confidence predictions are often inferred to be intrinsically disordered regions of proteins, which would be the case if Z* did not bind zinc. We use NMR and CD spectroscopy to show that a 25-51 segment of ZNF750, corresponding to the Z* domain, folds into a well-defined antiparallel ββα tertiary structure with a pM dissociation constant for zinc, and a thermal stability >80 oC. Of three alternative zinc ligand sets, Z* uses a CCHC rather than the expected CCHH motif. The switch in the last ligand maintains the folding topology and hydrophobic core of the classical ZNF motif. CCHC ZNFs are associated with protein-protein interactions but Z* binds DNA. Since the metal chelating site is on the other side of the molecule, it suggests functional preferences are a result of divergent evolution rather than physical constraints on the structure. The structure of Z* provides a context for understanding the domains DNA-binding properties and mutations associated with cancers. We expect other ZNFs currently classified as degenerate, are CCHC-type structures like Z*.

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“… 6 Evidence from melanocyte development indicate the possibility that WNT/β-catenin signaling orchestrates melanoma progression by regulating cell proliferation and invasion and modulating the immune microenvironment. 7 , 8 An increasing level of nuclear β-catenin has been shown to play a critical role in melanoma during disease progression. 9 , 10 In actively proliferating melanoma cells, nuclear β-catenin triggers the expression of microphthalmia-associated transcription factor that in turn activates the transcription of several downstream genes including VEGF.…”

Section: Introductionmentioning

confidence: 99%

Nomogram Incorporating the WNT/β-Catenin Signaling Pathway for Predicting the Survival of Cutaneous Melanoma

Zhou¹,

Wang²,

Pang³

et al. 2021

IJGM

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Background Accurate prediction of the survival of cutaneous melanoma (CM) permits the selection of the optimal treatment. Currently, the TNM stage has limitations in predicting the survival of CM. There is evidence that the WNT/β-catenin signaling pathway has the potential to predict the CM prognosis. However, it still needs further investigation. Objective This study aims to establish a nomogram incorporating the WNT/β-catenin signaling pathway to improve the predicted accuracy of the overall survival (OS) of CM. Methods Two hundred and eighty CM patients were recruited and followed up. The clinicopathological characteristics and the key genes of the WNT/β-catenin signaling pathway (VEGF, β-catenin, and DKK1) were chosen as potential variables associated with the OS. In the training cohort (n = 190), a nomogram was built to estimate the 1-, 3-, and 5-year OS, and its discriminations and calibrations were valid by the verification cohort (n = 90). The predicted accuracies of the nomogram with or without the Wnt/β-catenin pathway and TNM stage were compared. Results A nomogram integrating independent risk factors (ulceration, lymph node metastasis, distant metastasis, Breslow thickness, dermal mitoses, β-catenin, VEGF, and DKK1), which were evaluated by a multivariate analysis, was constructed to predict the 1-, 3-, and 5-year OS of CM patients. Good discrimination and calibration were obtained regardless of the training or validation datasets. The nomogram incorporating the Wnt/β-catenin signaling pathway showed the highest accuracy [area under the curve (AUC)=0.914, 0.852, 0.785] compared with the nomogram without the Wnt/β-catenin signaling pathway (AUC=0.693, 0.640, 0.615) and the TNM stage (AUC=0.726, 0.693, 0.673). Conclusion The prognostic value of the established nomogram incorporating the WNT/β-catenin signaling pathway was better than it without WNT/β-catenin signaling pathway and TNM stage, which might be beneficial in the development of optimal treatment options.

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ZNF750 inhibits the proliferation and invasion of melanoma cells through modulating the Wnt/b-catenin signaling pathway

Cited by 6 publications

References 32 publications

Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma

Sorting Transcriptomics Immune Information from Tumor Molecular Features Allows Prediction of Response to Anti-PD1 Therapy in Patients with Advanced Melanoma

NMR structure verifies the eponymous degenerate zinc finger domain of transcription factor ZNF750

Nomogram Incorporating the WNT/β-Catenin Signaling Pathway for Predicting the Survival of Cutaneous Melanoma

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