Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An Artificial CTCF Peptide Triggers Efficient Therapeutic Efficacy in Ocular Melanoma.

ABSTRACT: Although CCCTC binding factor (CTCF) has been demonstrated to play a variety of often contradictory roles in tumorigenesis, little is known about its function in the tumorigenesis of ocular melanoma. Here, we generated two artificial CTCF peptides (Decoy-CTCFs) combining the zinc finger domain of wild-type CTCF and artificial marker region. This Decoy-CTCF retained the DNA binding region but lost the functional regions of wild-type CTCF. Transferring artificial CTCF into ocular melanoma cells suppressed proliferation and migration in the tumor cells, while no effect was observed in normal cells. Intriguingly, we first showed that decoy-CTCF inhibited tumorigenesis by preventing the histone acetyltransferase EP300 from binding to the promoter of SELL. Thus SELL was a novel oncogene in the tumorigenesis of ocular melanoma. These studies provide efficient decoy CTCF-based therapeutic concept in malignant ocular melanoma and reveal the potential mechanism underlying decoy-based tumor therapy.

SUBMITTER: Wen X

PROVIDER: S-EPMC7394857 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

CANT1 lncRNA Triggers Efficient Therapeutic Efficacy by Correcting Aberrant lncing Cascade in Malignant Uveal Melanoma.

Project description:Uveal melanoma (UM) is an intraocular malignant tumor with a high mortality rate. Recent studies have shown the functions of long non-coding RNAs (lncRNAs) in tumorigenesis; thus, targeting tumor-specific lncRNA abnormalities has become an attractive approach for developing therapeutics to treat uveal melanoma. In this study, we identified a novel nuclear CANT1 lncRNA (CASC15-New-Transcript 1) that acts as a necessary UM suppressor. CANT1 significantly reduced tumor metastatic capacity and tumor formation, either in cell culture or in animals harboring tumor xenograft. Intriguingly, XIST lncRNA serves as a potential target of CANT1, and JPX or FTX lncRNA subsequently serves as a contextual hinge to activate a novel CANT1-JPX/FTX-XIST long non-coding (lncing) pathway in UM. Moreover, CANT1 triggers the expression of JPX and FTX by directly binding to their promoters and promoting H3K4 methylation. These observations delineate a novel lncing cascade in which lncRNAs directly build a lncing cascade without coding genes that aims to modulate UM tumorigenesis, thereby specifying a novel "lncing-cascade renewal" anti-tumor therapeutic strategy by correcting aberrant lncing cascade in uveal melanoma.

| S-EPMC5417793 | biostudies-literature

Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity.

Project description:Nonmutated tissue differentiation antigens expressed by tumors are attractive targets for cancer immunotherapy, but the consequences of a highly effective antitumor immune response on self-tissue have not been fully characterized. We found that the infusion of ex vivo expanded adoptively transferred melanoma/melanocyte-specific CD8+ T cells that mediated robust tumor killing also induced autoimmune destruction of melanocytes in the eye. This severe autoimmunity was associated with the up-regulation of MHC class I molecules in the eye and high levels of IFN-gamma derived from both adoptively transferred CD8+ T cells and host cells. Furthermore, ocular autoimmunity required the presence of the IFN-gamma receptor on target tissues. Data compiled from >200 eyes and tumors in 10 independently performed experiments revealed a highly significant correlation (P < 0.0001) between the efficacy of tumor immunotherapy and the severity of ocular autoimmunity. Administration of high doses of steroids locally mitigated ocular autoimmunity without impairing the antitumor effect. These findings have particular importance for immunotherapies directed against self-antigens and highlight the need for targeting unique tumor antigens not expressed in critical tissues.

| S-EPMC2409137 | biostudies-literature

Therapeutic Efficacy of Artificial Skin Produced by 3D Bioprinting.

Project description:The skin protects the body from external barriers. Certain limitations exist in the development of technologies to rapidly prepare skin substitutes that are therapeutically effective in surgeries involving extensive burns and skin transplantation. Herein, we fabricated a structure similar to the skin layer by using skin-derived decellularized extracellular matrix (dECM) with bioink, keratinocytes, and fibroblasts using 3D-printing technology. The therapeutic effects of the produced skin were analyzed using a chimney model that mimicked the human wound-healing process. The 3D-printed skin substitutes exhibited rapid re-epithelialization and superior tissue regeneration effects compared to the control group. These results are expected to aid the development of technologies that can provide customized skin-replacement tissues produced easily and quickly via 3D-printing technology to patients.

| S-EPMC8467964 | biostudies-literature

PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells.

Project description:Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug.

| S-EPMC8861012 | biostudies-literature

Efficient Artificial Light-Harvesting System Based on Supramolecular Peptide Nanotubes in Water.

Project description:Artificial light-harvesting systems in aqueous media which mimic nature are of significant importance; however, they are often restrained by the solubility and the undesired aggregation-caused quenching effect of the hydrophobic chromophores. Here, we report a generalized strategy toward the construction of efficient artificial light-harvesting systems based on supramolecular peptide nanotubes in water. By molecularly aligning the hydrophobic chromophores along the nanotubes in a slipped manner, an artificial light-harvesting system with a two-step sequential Förster resonance energy transfer process is successfully fabricated, showing an energy transfer efficiency up to 95% and a remarkably high fluorescence quantum yield of 30%, along with high stability. Furthermore, the spectral emission could be continuously tuned from blue through green to orange, as well as outputted as a white light continuum with a fluorescence quantum yield of 29.9%. Our findings provide a versatile approach of designing efficient artificial light-harvesting systems and constructing highly emissive organic materials in aqueous media.

| S-EPMC8172009 | biostudies-literature

Peptide Vaccines in Melanoma: Chemical Approaches towards Improved Immunotherapeutic Efficacy.

Project description:Cancer of the skin is by far the most common of all cancers. Although the incidence of melanoma is relatively low among skin cancers, it can account for a high number of skin cancer deaths. Since the start of deeper insight into the mechanisms of melanoma tumorigenesis and their strong interaction with the immune system, the development of new therapeutical strategies has been continuously rising. The high number of melanoma cell mutations provides a diverse set of antigens that the immune system can recognize and use to distinguish tumor cells from normal cells. Peptide-based synthetic anti-tumor vaccines are based on tumor antigens that elicit an immune response due to antigen-presenting cells (APCs). Although targeting APCs with peptide antigens is the most important assumption for vaccine development, peptide antigens alone are poorly immunogenic. The immunogenicity of peptide antigens can be improved not only by synthetic modifications but also by the assistance of adjuvants and/or delivery systems. The current review summarizes the different chemical approaches for the development of effective peptide-based vaccines for the immunotherapeutic treatment of advanced melanoma.

| S-EPMC9963291 | biostudies-literature

Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

Project description:BACKGROUND:BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM) and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome. DESIGN:To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM) including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds. RESULTS:Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p?=?0.059). Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p?=?.003). Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs). Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition. CONCLUSION:Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome), which could be a useful clinical marker for constitutive BAP1 inactivation.

| S-EPMC3335872 | biostudies-literature

histone lactylation in ocular melanoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-04 | GSE242019 | GEO

Efficient Therapeutic Delivery by a Novel Cell-Penetrating Peptide Derived from Acinus.

Project description:In this study, we have identified a novel cell-penetrating sequence, termed hAP10, from the C-terminus of the human protein Acinus. hAP10 was able to efficiently enter various normal and cancerous cells, likely through an endocytosis pathway, and to deliver an EGFP cargo to the cell interior. Cell penetration of a peptide, hAP10DR, derived from hAP10 by mutation of an aspartic acid residue to an arginine was dramatically increased. Interestingly, a peptide containing a portion of the heptad leucine repeat region domain of the survival protein AAC-11 (residues 377-399) fused to either hAP10 or hAP10DR was able to induce tumor cells, but not normal cells, death both ex vivo on Sézary patients' circulating cells and to inhibit tumor growth in vivo in a sub-cutaneous xenograft mouse model for the Sézary syndrome. Combined, our results indicate that hAP10 and hAP10DR may represent promising vehicles for the in vitro or in vivo delivery of bioactive cargos, with potential use in clinical settings.

| S-EPMC7408964 | biostudies-literature

Combined Inhibition of Gaq and MEK Enhances Therapeutic Efficacy in Uveal Melanoma

Project description:We developed an isogenic melanocytic cellular system and systematically examined the hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (e.g. L129Q) in human uveal melanoma. Biochemical and cell viability assays validated YM-254890 as a potent inhibitor of cell signaling and growth. Human uveal melanoma cells and mouse models recapitulated this finding, indicating that YM is also effective in vivo. Combination of YM and MEK inhibition leads to further decreases in MAPK pathway gene expression and cell viability. Furthermore, our cellular and mouse models show that combination leads to long term signaling inhibition and significant decreases in tumor burden.

2020-12-31 | GSE160112 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data