Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338515 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-Wide Scan for Genetic Variants Associated with Early Onset Prostate Cancer
| PRJNA338514 | ENA
Project description:LINC00920 is a tumor-associated lncRNA identified in the transcriptome dataset of the International Cancer Genome Consortium-Early Onset Prostate Cancer (ICGC-EOPC) cohort. SiRNA-mediated knockdown of LINC00920 negatively affected proliferation, colony formation, and migration of PC-3 prostate cancer cells. Genome-wide expression profiling was performed to identify cellular pathways affected by LINC00920.
2020-07-20 | GSE130978 | GEO
Project description:Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer deaths in men. GWAS studies have identified variants associated with prostate cancer susceptibility, however, mechanistic and functional validation of these mutations are lacking. Mitochondrial energy metabolism plays an important role in the onset and development of cancer. A missense variant was identified in the ELAC2 gene, which encodes a dually localized nuclear and mitochondrial RNA processing enzyme, with predicted impact on metabolism and tumorigenesis. We used CRISPR/Cas9 genome editing to introduce this variant into the mouse Elac2 gene as well as to generate a prostate-specific gene knockout of Elac2. The mutations caused enlargement and inflammation in the prostate and nodule formation. Multi-omic profiling revealed defects in RNA and energy metabolism that activated proinflammatory and tumorigenic pathways as a consequence of impaired processing of mitochondrial and nuclear encoded non-coding RNAs and reduced protein synthesis. The Elac2 variant or knockout mice on the background of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model show that Elac2 mutation with a secondary genetic insult exacerbated the onset and progression of prostate cancer and led to metastasis. Our systems biology analyses reveal a miRNA-mediated molecular mechanism by which specific non-coding RNAs elicit metabolic changes that drive prostate tumorigenesis and metastasis. We conclude that the ELAC2 variant is a predisposing factor for prostate cancer and provide a detailed molecular mechanism and physiologically relevant models of this cancer.
2023-04-19 | PXD033891 | Pride
Project description:To date, genome-wide association studies (GWAS) have revealed over 200 genetic risk loci associated with prostate cancer; yet, true disease-causing variants in gene regulatory regions remain elusive. Identification of causal variants and their targets from association signals relevant to prostate cancer is complicated by high linkage disequilibrium and limited availability of functional genomics data for specific tissue/cell types. Here, we integrated statistical fine-mapping and functional annotation from prostate-specific epigenomic profiles, high resolution 3D genome features, and quantitative trait loci data to distinguish causal variants from associations and identify target genes they regulate. Our fine-mapping analysis yielded 1,892 likely causal variants, and multiscale functional annotation linked them to 406 target genes. We prioritized rs10486567, located in an enhancer, as a genome-wide top-ranked SNP and predicted HOTTIP as its target. Deletion of the rs10486567-associated enhancer in prostate cancer cells decreased their capacity for invasive migration. HOTTIP overexpression in an enhancer-KO cell line rescued defective invasive migration. Furthermore, we found that rs10486567 regulates HOTTIP through allele-specific long- range chromatin interaction.
2023-02-25 | GSE197819 | GEO
Project description:To date, genome-wide association studies (GWAS) have revealed over 200 genetic risk loci associated with prostate cancer; yet, true disease-causing variants in gene regulatory regions remain elusive. Identification of causal variants and their targets from association signals relevant to prostate cancer is complicated by high linkage disequilibrium and limited availability of functional genomics data for specific tissue/cell types. Here, we integrated statistical fine-mapping and functional annotation from prostate-specific epigenomic profiles, high resolution 3D genome features, and quantitative trait loci data to distinguish causal variants from associations and identify target genes they regulate. Our fine-mapping analysis yielded 1,892 likely causal variants, and multiscale functional annotation linked them to 406 target genes. We prioritized rs10486567, located in an enhancer, as a genome-wide top-ranked SNP and predicted HOTTIP as its target. Deletion of the rs10486567-associated enhancer in prostate cancer cells decreased their capacity for invasive migration. HOTTIP overexpression in an enhancer-KO cell line rescued defective invasive migration. Furthermore, we found that rs10486567 regulates HOTTIP through allele-specific long- range chromatin interaction.
2023-02-25 | GSE197818 | GEO
Project description:To date, genome-wide association studies (GWAS) have revealed over 200 genetic risk loci associated with prostate cancer; yet, true disease-causing variants in gene regulatory regions remain elusive. Identification of causal variants and their targets from association signals relevant to prostate cancer is complicated by high linkage disequilibrium and limited availability of functional genomics data for specific tissue/cell types. Here, we integrated statistical fine-mapping and functional annotation from prostate-specific epigenomic profiles, high resolution 3D genome features, and quantitative trait loci data to distinguish causal variants from associations and identify target genes they regulate. Our fine-mapping analysis yielded 1,892 likely causal variants, and multiscale functional annotation linked them to 406 target genes. We prioritized rs10486567, located in an enhancer, as a genome-wide top-ranked SNP and predicted HOTTIP as its target. Deletion of the rs10486567-associated enhancer in prostate cancer cells decreased their capacity for invasive migration. HOTTIP overexpression in an enhancer-KO cell line rescued defective invasive migration. Furthermore, we found that rs10486567 regulates HOTTIP through allele-specific long- range chromatin interaction.
2023-02-25 | GSE197816 | GEO
Project description:To date, genome-wide association studies (GWAS) have revealed over 200 genetic risk loci associated with prostate cancer; yet, true disease-causing variants in gene regulatory regions remain elusive. Identification of causal variants and their targets from association signals relevant to prostate cancer is complicated by high linkage disequilibrium and limited availability of functional genomics data for specific tissue/cell types. Here, we integrated statistical fine-mapping and functional annotation from prostate-specific epigenomic profiles, high resolution 3D genome features, and quantitative trait loci data to distinguish causal variants from associations and identify target genes they regulate. Our fine-mapping analysis yielded 1,892 likely causal variants, and multiscale functional annotation linked them to 406 target genes. We prioritized rs10486567, located in an enhancer, as a genome-wide top-ranked SNP and predicted HOTTIP as its target. Deletion of the rs10486567-associated enhancer in prostate cancer cells decreased their capacity for invasive migration. HOTTIP overexpression in an enhancer-KO cell line rescued defective invasive migration. Furthermore, we found that rs10486567 regulates HOTTIP through allele-specific long- range chromatin interaction.
2023-02-25 | GSE197817 | GEO
Project description:Background: Numerous germline genetic variants are associated with prostate cancer risk, but their biological role is not well understood. One possibility is that these variants influence gene expression in prostate tissue. We therefore examined the association of prostate cancer risk variants with the expression of genes nearby and genome-wide. Methods: We generated mRNA expression data for 20,254 genes with the Affymetrix GeneChip Human Gene 1.0 ST microarray from normal prostate (N=160) and prostate tumor (N=264) tissue from participants of the Physicians’ Health Study and Health Professionals Follow-up Study. With linear models, we tested the association of 39 risk variants with nearby genes and all genes, and the association of each variant with canonical pathways using a global test. Results: In addition to confirming previously reported associations, we detected several new significant (p<0.05) associations of variants with the expression of nearby genes including C2orf43, ITGA6, MLPH, CHMP2B, BMPR1B, and MTL5. Genome-wide, four genes (MSMB, NUDT11, NEFM, KLHL33) were significantly associated after accounting for multiple comparisons for each SNP (p<2.5x10-6). Many more genes had a false discovery rate <10%, including SRD5A1 and PSCA, and we observed significant associations with pathways in tumor tissue. Conclusions: The risk variants were associated with several genes, including promising prostate cancer candidates and lipid metabolism pathways, suggesting mechanisms for their impact on disease. These genes should be further explored in biological and epidemiological studies. Impact: Determining the biological role of these variants can lead to improved understanding of prostate cancer etiology and identify new targets for chemoprevention.
2014-12-01 | GSE62872 | GEO