Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of the DNA damage response and melanoma susceptibility by NCOA3

ABSTRACT: NCOA3 has important roles in melanoma as a potential diagnostic and susceptibility marker, and as a target for therapy

ORGANISM(S): Homo sapiens

PROVIDER: GSE156062 | GEO | 2021/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regulation of the DNA damage response and melanoma susceptibility by NCOA3

Project description:Regulation of the DNA damage response and melanoma susceptibility by NCOA3

| PRJNA656562 | ENA

Nuclear Receptor Coactivator NCOA3 Regulates UV Radiation-Induced DNA Damage and Melanoma Susceptibility.

Project description:Melanoma occurs as a consequence of inherited susceptibility to the disease and exposure to UV radiation (UVR) and is characterized by uncontrolled cellular proliferation and a high mutational load. The precise mechanisms by which UVR contributes to the development of melanoma remain poorly understood. Here we show that activation of nuclear receptor coactivator 3 (NCOA3) promotes melanomagenesis through regulation of UVR sensitivity, cell-cycle progression, and circumvention of the DNA damage response (DDR). Downregulation of NCOA3 expression, either by genetic silencing or small-molecule inhibition, significantly suppressed melanoma proliferation in melanoma cell lines and patient-derived xenografts. NCOA3 silencing suppressed expression of xeroderma pigmentosum C and increased melanoma cell sensitivity to UVR. Suppression of NCOA3 expression led to activation of DDR effectors and reduced expression of cyclin B1, resulting in G2-M arrest and mitotic catastrophe. A SNP in NCOA3 (T960T) reduced NCOA3 protein expression and was associated with decreased melanoma risk, given a significantly lower prevalence in a familial melanoma cohort than in a control cohort without cancer. Overexpression of wild-type NCOA3 promoted melanocyte survival following UVR and was accompanied by increased levels of UVR-induced DNA damage, both of which were attenuated by overexpression of NCOA3 (T960T). These results describe NCOA3-regulated pathways by which melanoma can develop, with germline NCOA3 polymorphisms enabling enhanced melanocyte survival in the setting of UVR exposure, despite an increased mutational burden. They also identify NCOA3 as a novel therapeutic target for melanoma. SIGNIFICANCE: This study explores NCOA3 as a regulator of the DDR and a therapeutic target in melanoma, where activation of NCOA3 contributes to melanoma development following exposure to ultraviolet light.

| S-EPMC8178194 | biostudies-literature

Genetic architecture of susceptibility to melanoma

Project description:Genetic architecture of susceptibility to melanoma

| PRJNA554944 | ENA

Genetic architecture of susceptibility to melanoma

Project description:Genetic architecture of susceptibility to melanoma

| PRJNA554943 | ENA

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

Project description:Orphan nuclear receptor Esrrb is vital in maintaining ES cells and like Oct4, Sox2 and Nanog is essential for self-renewal and pluripotency. Esrrb functions in somatic cells via LBD/AF-2-dependent coactivator recruitment to target genes. Here we show that in ES cells coactivator recruitment is similarly required and identify Ncoa3 as the Esrrb coactivator needed for activation of its target genes. Ncoa3 is essential for self-renewal and the induction of pluripotency in reprogramming, and genome-wide analysis of Ncoa3 binding reveals extensive overlap with Esrrb and pluripotency factors along with marks of active genes. Mechanistically, we show Ncoa3 is specifically required to bridge RNApol2 to Esrrb. We thus identify a new member of the ES pluripotency network and describe Esrrb and Ncoa3 as key factors linking core pluripotency factors to the general transcription machinery.

2012-10-02 | GSE40192 | GEO

Global gene expression analysis of Ncoa3 knockdown in mouse embryonic stem cells

2012-10-02 | E-GEOD-40192 | biostudies-arrayexpress

Rare germline copy number variations and disease susceptibility in familial melanoma

Project description:Mounting evidence suggests that copy number variations (CNVs) can contribute to cancer susceptibility. The main goal of this study was to evaluate the role of germline CNVs in melanoma predisposition in high-risk melanoma families. We used genome-wide tiling comparative genomic hybridization and SNP arrays to characterize CNVs in 335 individuals (240 melanoma cases) from American melanoma-prone families (22 with germline CDKN2A or CDK4 mutations). We found that the global burden of overall CNVs (or deletions or duplications separately) was not significantly associated with case-control or CDKN2A/CDK4 mutation status after accounting for the familial dependence. However, we identified several rare CNVs that either involved known melanoma genes (e.g. PARP1, CDKN2A) or co-segregated with melanoma (duplication on 10q23.23, 3p12.2 and deletions on 8q424.3, 2q22.1) in families without mutations in known melanoma high-risk genes. Some of these CNVs were correlated with expression changes in disrupted genes based on RNASeq data from a subset of melanoma cases included in the CNV study. These results suggest that rare co-segregating CNVs may influence melanoma susceptibility in some melanoma-prone families and genes found in our study warrant further evaluation in future genetic analyses of melanoma.

2016-12-01 | GSE85010 | GEO

NCOA3 upregulates MUC4 and MUC1 transcriptionally and through post-translational stability during pancreatic cancer development

Project description:Stable knock down of NCOA3 in PC cell lines resulted in significant downregulation of the two most differentially expressed MUCs in PC, MUC4 and MUC1. NCOA3 creates pro-inflammatory conditions by up-regulating chemokines like CXCL1, 2, 5 and CCL20

2013-12-19 | GSE51482 | GEO

Uveal Melanoma Immunogenomics Predict Immunotherapy Resistance and Susceptibility

Project description:Uveal Melanoma Immunogenomics Predict Immunotherapy Resistance and Susceptibility

| PRJNA989355 | ENA

Uveal Melanoma Immunogenomics Predict Immunotherapy Resistance and Susceptibility

Project description:Uveal Melanoma Immunogenomics Predict Immunotherapy Resistance and Susceptibility

| PRJNA989356 | ENA