SNP rs4971059 Predisposes to Breast Carcinogenesis and Chemoresistance by Powering DNA Replication [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA736667 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14777647.fastq.gz | Fastqsanger.gz | |||
| SRR14777648.fastq.gz | Fastqsanger.gz | |||
| SRR14777649.fastq.gz | Fastqsanger.gz | |||
| SRR14777650.fastq.gz | Fastqsanger.gz |
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Project description:SNP rs4971059 Predisposes to Breast Carcinogenesis and Chemoresistance by Powering DNA Replication.
| PRJNA736637 | ENA
Project description:SNP rs4971059 Predisposes to Breast Carcinogenesis and Chemoresistance by Powering DNA Replication [ChIP-seq]
| PRJNA736668 | ENA
Project description:Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single-nucleotide polymorphism (SNP) rs4971059, one of the 65 new breast cancer risk loci identified in a recent genome-wide association analysis, locates at the 6th intron of TRIM46 that functions as an active enhancer. We find that G to A polymorphic switch of the rs4971059 allele augments its chromosomal interaction with the promoter and boosts its enhancer activity. Accordingly, cells carry SNP[A] rs4971059 display an elevated TRIM46 expression. We find that TRIM46 is a ubiquitin ligase that targets HDAC1 for ubiquitination and degradation. Integrative genomic and transcriptomic studies reveal that the TRIM46-HDAC1 axis regulates a panel of genes including ones that are critically involved in DNA replication and repair. Consistently, depletion of TRIM46 impedes S phase progression and sensitizes cells to DNA-damaging reagents. We demonstrate that TRIM46 promotes breast cancer cell proliferation and chemoresistance in vitro and accelerates breast cancer growth in vivo. Importantly, TRIM46 is frequently overexpressed in breast carcinomas, and its level of expression is negatively correlated with that of HDAC1 as well as with higher histological grades and worse prognosis of breast cancer patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance, supporting the pursuit of TRIM46 as a potential target for breast cancer intervention.
2021-06-11 | GSE176537 | GEO
Project description:Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single-nucleotide polymorphism (SNP) rs4971059, one of the 65 new breast cancer risk loci identified in a recent genome-wide association analysis, locates at the 6th intron of TRIM46 that functions as an active enhancer. We find that G to A polymorphic switch of the rs4971059 allele augments its chromosomal interaction with the promoter and boosts its enhancer activity. Accordingly, cells carry SNP[A] rs4971059 display an elevated TRIM46 expression. We find that TRIM46 is a ubiquitin ligase that targets HDAC1 for ubiquitination and degradation. Integrative genomic and transcriptomic studies reveal that the TRIM46-HDAC1 axis regulates a panel of genes including ones that are critically involved in DNA replication and repair. Consistently, depletion of TRIM46 impedes S phase progression and sensitizes cells to DNA-damaging reagents. We demonstrate that TRIM46 promotes breast cancer cell proliferation and chemoresistance in vitro and accelerates breast cancer growth in vivo. Importantly, TRIM46 is frequently overexpressed in breast carcinomas, and its level of expression is negatively correlated with that of HDAC1 as well as with higher histological grades and worse prognosis of breast cancer patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance, supporting the pursuit of TRIM46 as a potential target for breast cancer intervention.
2021-06-11 | GSE176536 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-06-11 | GSE176538 | GEO
Project description:Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single-nucleotide polymorphism (SNP) rs4971059, one of 65 new breast cancer risk loci identified in a recent genome-wide association study (GWAS), functions as an active enhancer of TRIM46 expression. Recreating the G-to-A polymorphic switch caused by the SNP via CRISPR/Cas9-mediated homologous recombination leads to an overt upregulation of TRIM46. We find that TRIM46 is a ubiquitin ligase that targets histone deacetylase HDAC1 for ubiquitination and degradation, and that the TRIM46-HDAC1 axis regulates a panel of genes, including ones critically involved in DNA replication and repair. Consequently, TRIM46 promotes breast cancer cell proliferation and chemoresistance in vitro and accelerates tumor growth in vivo. Moreover, TRIM46 is frequently overexpressed in breast carcinomas, and its expression is correlated with lower HDAC1 expression, higher histological grades, and worse prognosis of the patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance, and support the pursuit of TRIM46 as a potential target for breast cancer intervention.
| S-SCDT-EMBOJ-2021-107974 | biostudies-other
Project description:Because gastric cancer cells already had genetic and epigenetic alterations which can affect the gastric carcinogenesis, we tried to characterize genetic and epigenetic changes during gastric carcinogenesis. To do this, we performed SNP array.
2017-09-01 | GSE55153 | GEO
Project description:Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assesed to described chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (60% of cases) in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen, and paraffin embedded lung tumor samples Copy number analysis of Affymetrix 500K SNP arrays was performed for 33 lung tumor samples, including lung precursor metaplasia, lung tumors and cell lines. Six samples were also hybridized on the Affymetrix SNP 6.0 array
2014-12-10 | E-GEOD-62407 | biostudies-arrayexpress
Project description:A core task to understand the consequences of non-coding single nucleotide polymorphisms (SNP) is to identify their genotype specific binding of transcription factor (TF). Here, we generate a large-scale TF-SNP interaction map for a selection of 116 colorectal cancer (CRC) risk loci and validated TF binding to 10 putatively functional SNPs. Our data further revealed TF binding complexity adjacent to the 116 risk loci, adding an additional layer of understanding to regulatory networks associated with CRC relevant loci.
2017-02-23 | PXD004435 | Pride
Project description:We present the first computational approach to reconstruct the sequence of copy number alterations driving carcinogenesis from the analysis of several tumor samples of a same patient. Applied to BAC array-CGH and SNP array data from bladder and breast cancers, this method proved highly valuable to establish the clonal relationships between primary tumors and recurrences and to identify the chromosome aberrations at the initiation of tumorigenesis.
2009-12-01 | GSE19189 | GEO