Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4

ABSTRACT: Single nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4

PROVIDER: PRJNA560419 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR9975246.fastq.gz	Fastqsanger.gz
	SRR9975247.fastq.gz	Fastqsanger.gz
	SRR9975248.fastq.gz	Fastqsanger.gz

Items per page:

1 - 3 of 3

Similar Datasets

Single nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4

Project description:A prostate cancer risk single nucleotide polymorphism (SNP), rs13426236, is significantly associated with melanophilin (MLPH) expression. To functionally characterize role of the rs13426236 in prostate cancer, we first performed splicing-specific expression Quantitative Trait Loci (eQTL) analysis and refined the significant association of rs13426236 allele G with an increased expression of MLPH splicing variant 4 (V4) (P= 7.61E-5) but not other protein-coding variants (V1-V3) (P>0.05). We then performed an allele-specific reporter assay to determine if SNP-containing sequences functioned as active enhancer. Compared to allele A, allele G of rs13426236 showed significantly higher luciferase activity on the promoter of the splicing transcript V4 (P <0.03) but not on promoter of transcript V1 (P>0.05) in two prostate cancer cell lines (DU145 and 22Rv1). Transfection of MLPH splicing variants showed stronger effect of transcript V4 than V1 on promoting cell proliferation, invasion and anti-apoptotic activities. RNA profiling analysis demonstrated that transcript V4 overexpression caused significant expression changes in glycosylation/glycoprotein and metal-binding gene ontology pathways (FDR<0.01). We also found that both transcripts V4 and V1 were significantly up-regulated in prostate adenocarcinoma (P<2.49E-6) but only transcript V4 up-regulation was associated with poor recurrence free survival (P=0.028, HR=1.63, 95%CI=1.05-2.42) in The Cancer Genome Atlas (TCGA) data. This study provides strong evidence showing that prostate cancer risk SNP rs13426236 up-regulates expression of MLPH transcript V4, which may function as a candidate oncogene in prostate cancer.

2019-08-16 | GSE135888 | GEO

Single-nucleotide polymorphism rs13426236 contributes to an increased prostate cancer risk via regulating MLPH splicing variant 4.

Project description:A prostate cancer risk single-nucleotide polymorphism (SNP), rs13426236, is significantly associated with melanophilin (MLPH) expression. To functionally characterize role of the rs13426236 in prostate cancer, we first performed splicing-specific expression quantitative trait loci analysis and refined the significant association of rs13426236 allele G with an increased expression of MLPH splicing transcript variant 4 (V4) (P = 7.61E-5) but not other protein-coding variants (V1-V3) (P > .05). We then performed an allele-specific reporter assay to determine if SNP-containing sequences functioned as an active enhancer. Compared to allele A, allele G of rs13426236 showed significantly higher luciferase activity on the promoter of the splicing transcript V4 (P < .03) but not on the promoter of transcript V1 (P > .05) in two prostate cancer cell lines (DU145 and 22Rv1). Cell transfection assays showed stronger effect of transcript V4 than V1 on promoting cell proliferation, invasion, and antiapoptotic activities. RNA profiling analysis demonstrated that transcript V4 overexpression caused significant expression changes in glycosylation/glycoprotein and metal-binding gene ontology pathways (FDR < 0.01). We also found that both transcripts V4 and V1 were significantly upregulated in prostate adenocarcinoma (P ≤ 2.49E-6) but only transcript V4 upregulation was associated with poor recurrence-free survival (P = .028, hazard ratio = 1.63, 95% confidence interval = 1.05-2.42) in The Cancer Genome Atlas data. This study provides strong evidence showing that prostate cancer risk SNP rs13426236 upregulates expression of MLPH transcript V4, which may function as a candidate oncogene in prostate cancer.

| S-EPMC7219604 | biostudies-literature

A biallelic multiple nucleotide length polymorphism explains functional causality at 5p15.33 prostate cancer risk locus [RNA-Seq]

Project description:To date, single-nucleotide polymorphisms (SNPs) have been the most intensively investigated class of polymorphisms in genome wide associations studies (GWAS), however, other classes such as insertion-deletion or multiple nucleotide length polymorphism (MNLPs) may also confer disease risk. Multiple reports have shown that the 5p15.33 prostate cancer (PCa) risk region is a particularly strong expression quantitative trait locus (eQTL) for IRX4 transcripts. Here, we demonstrate using epigenome and genome editing that a biallelic (47bp/21bp) MNLP is the causal variant regulating IRX4 transcript levels. In LNCaP PCa cells (homozygous for the short allele), a single copy knock-in of the long allele potently alters the chromatin state, enabling de novo functional binding of the androgen receptor (AR) associated with increased chromatin accessibility, H3K27 acetylation, and ~3-fold upregulation of IRX4 expression. We further show that an MNLP is amongst the strongest candidate susceptibility variants at two additional PCa risk loci. We estimated that at least 5% of PCa risk loci could be explained by functional non-SNP causal variants, which may have broader implications for other cancers GWAS. More generally, our results underscore the importance of investigating other classes of inherited variation as causal mediators of human traits.

2023-07-11 | GSE231747 | GEO

A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ATAC-Seq]

2023-07-11 | GSE231750 | GEO

A biallelic multiple nucleotide length polymorphism explains functional causality at the 5p15.33 prostate cancer risk locus [ChIP-Seq]

2023-07-11 | GSE231748 | GEO

GSTM3 single nucleotide polymorphism (rs7483) associated with peripheral BMC expression in Alzheimer disease

2009-01-12 | GSE4227 | GEO

A non-coding single nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation

Project description:Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single nucleotide polymorphism rs55705857 (A>G), which confers a 6-fold increased risk of IDH-mutant low-grade glioma (LGG) and is amongst the highest genetic associations with cancer. By fine-mapping the locus, we reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. To functionally test rs55705857, we generated an IDH1R132H-driven LGG mouse model and show that mutating the highly conserved, orthologous mouse rs55705857 locus dramatically accelerated tumor development from 463 to 172 days and increased penetrance from 30% to 75%. Overall, our work generates new LGG models and reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG-patients.

2022-09-12 | GSE206875 | GEO

GSTM3 single nucleotide polymorphism (rs7483) associated with peripheral BMC expression in Alzheimer disease

Project description:Comparisons between the sample groups (normal elderly control (NEC) and Alzheimer disease (AD)) allowed the identification of genes with disease expression patterns associated with the glutathione S-transferase M3 single nucleotide polymorphism rs7483. Keywords: biological repeat Peripheral blood mononuclear cells (BMC) were obtained from normal elderly control (NEC) and Alzheimer disease (AD) subjects. Targets from biological replicates of NEC (n=18) and AD (n=16) were generated and the expression profiles were determined using the NIA Human MGC cDNA microarray.

2010-06-24 | E-GEOD-4227 | biostudies-arrayexpress

Gene-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia.

Project description:Gene-expression profiling according to the Wilms tumor 1 (WT1) single nucleotide polymorphism rs16754 in adult de novo cytogenetically normal acute myeloid leukemia.

2012-06-09 | E-TABM-1165 | biostudies-arrayexpress

A single nucleotide polymorphism in the promoter of a hairpin RNA contributes to Alternaria leaf spot resistance in apple (Malus × domestica Borkh.)

Project description:A single nucleotide polymorphism in the promoter of a hairpin RNA contributes to Alternaria leaf spot resistance in apple (Malus × domestica Borkh.)

| PRJNA475703 | ENA

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