Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA212100 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The mechanism by which rs6983267 at 8q24.21 increases cancer risk is unclear for the lack of protein?coding genes in the region although the variant is strongly associated with cancer pathogenesis. Here we identify long non-coding RNAs (lncRNAs) near the 8q24 region and show that expression of lncRNA CARLo-5 is significantly correlated with the risk allele of the cancer-associated variant rs6883267. We further report that the 8q24 enhancer region including the variant directly interacts with active regulatory region of the lncRNA CARLo-5 promtoer. Finally, we demonstrate that CARLo-5 has an oncogenic function by regulating cell proliferation and cell-cycle. Our data provide new insight of disease-related variants in a gene desert. Comparison and identification of cell cycle-related genes differentially expressed by CARLo-5 knockdown using Nanostring analysis in HCT116 cells.
2014-03-05 | E-GEOD-48877 | biostudies-arrayexpress
Project description:The mechanism by which rs6983267 at 8q24.21 increases cancer risk is unclear for the lack of protein?coding genes in the region although the variant is strongly associated with cancer pathogenesis. Here we identify long non-coding RNAs (lncRNAs) near the 8q24 region and show that expression of lncRNA CARLo-5 is significantly correlated with the risk allele of the cancer-associated variant rs6883267. We further report that the 8q24 enhancer region including the variant directly interacts with active regulatory region of the lncRNA CARLo-5 promtoer. Finally, we demonstrate that CARLo-5 has an oncogenic function by regulating cell proliferation and cell-cycle. Our data provide new insight of disease-related variants in a gene desert.
2014-03-05 | GSE48877 | GEO
Project description:Chromosome instability is a key event in cancer progression. The essential histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function, but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including at the 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Intriguingly, in many cancers, transcription of lncRNAs is upregulated and correlates with poor prognosis, therapeutic resistance, and cancer recurrence in patients. Here, we report that the transcription of chromosome 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the chromatin landscape of the 8q24 locus. We report that transcription of oncogenic ncRNAs and associated R-loop formation at the 8q24 genomic locus results in the recruitment of H3.3 chaperone-CENP-A histone variant complexes to 8q24. Finally, we demonstrate that a transgene cassette which encodes a specific oncogenic lncRNA from the 8q24 region integrated into a naïve chromosome locus, recruits CENP-A to the new location specifically in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory in human cancer cells.
2022-03-09 | GSE180957 | GEO
Project description:Chromosome instability is a key event in cancer progression. The essential histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function, but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including at the 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Intriguingly, in many cancers, transcription of lncRNAs is upregulated and correlates with poor prognosis, therapeutic resistance, and cancer recurrence in patients. Here, we report that the transcription of chromosome 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the chromatin landscape of the 8q24 locus. We report that transcription of oncogenic ncRNAs and associated R-loop formation at the 8q24 genomic locus results in the recruitment of H3.3 chaperone-CENP-A histone variant complexes to 8q24. Finally, we demonstrate that a transgene cassette which encodes a specific oncogenic lncRNA from the 8q24 region integrated into a naïve chromosome locus, recruits CENP-A to the new location specifically in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory in human cancer cells.
2022-03-09 | GSE180938 | GEO
Project description:Chromosome instability is a key event in cancer progression. The essential histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function, but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including at the 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Intriguingly, in many cancers, transcription of lncRNAs is upregulated and correlates with poor prognosis, therapeutic resistance, and cancer recurrence in patients. Here, we report that the transcription of chromosome 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the chromatin landscape of the 8q24 locus. We report that transcription of oncogenic ncRNAs and associated R-loop formation at the 8q24 genomic locus results in the recruitment of H3.3 chaperone-CENP-A histone variant complexes to 8q24. Finally, we demonstrate that a transgene cassette which encodes a specific oncogenic lncRNA from the 8q24 region integrated into a naïve chromosome locus, recruits CENP-A to the new location specifically in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory in human cancer cells.
2022-03-09 | GSE180923 | GEO
Project description:An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that this region is a transcriptional enhancer, that the risk region physically interacts with the MYC proto-oncogene, and that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2). These data provide strong support for a biological mechanism underlying this non-protein coding risk variant. Total RNA and genomic DNA were isolated from colon tissue in 5 individuals. cDNA and DNA were analyzed on separate tracks, with the genomic DNA used to identify sprurious cross-hybridization
2010-05-18 | E-GEOD-16228 | biostudies-arrayexpress
Project description:An inherited variant on chromosome 8q24, rs6983267, is significantly associated with cancer pathogenesis. We present evidence that this region is a transcriptional enhancer, that the risk region physically interacts with the MYC proto-oncogene, and that the alleles of rs6983267 differentially bind transcription factor 7-like 2 (TCF7L2). These data provide strong support for a biological mechanism underlying this non-protein coding risk variant.
2009-06-08 | GSE16228 | GEO
Project description:To determine if there is a physical interaction between the FOXF1 promoter and putative enhancer sequences ~250kb upstream of the promoter chromosome conformation capture-on-chip (4C) analysis was performed. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. 4C analysis using 16q24.1 specific 3x720K arrays demonstrated physical interaction between the FOXF1 promoter and distant putative regulatory sequences, about 250 kb upstream in human pulomonary microvascular endothelial cells; 2 biological replicates performed; this chromatin looping was not detected in lymphoblasts that do not express FOXF1 and hence serve as a negative control.
2012-07-10 | E-GEOD-39256 | biostudies-arrayexpress
Project description:Multiple myeloma (MM) ranks the second most prevalent haematological malignancy globally. Despite advancements in managing MM, it remains incurable due to the high genetic heterogeneity leading to treatment resistance and disease severity. One key drug resistance associated signalling pathway often hyperactivated in MM patients is the non-canonical NF- κB/p52 pathway. Additionally, dysregulated expression of various oncogenic long non-coding RNAs (lncRNAs) have been observed in MM. This study aims to examine the potential link between ncNF-κB activation and dysregulated lncRNA expression controlling the chemoresistance and oncogenic progression of MM. Using mutant MM cell lines as model system and omics data from MM patients, we identified a novel p52 regulated lncRNA enriched in high-risk MM patients. The lncRNA termed PLUM (PRC2 associated LncRNA regulating UPR in MM) is found to interact directly with PRC2 complex to mediate myeloma progression and chemoresistance. RACE (Rapid amplification of cDNA ends) analysis revealed PLUM exists in three main isoforms in drug resistant multiple myeloma cell lines (MMCLs), comprising 8 exons without coding potential. Functionally, PLUM exerts its oncogenic and drug resistance properties in vivo and in vitro via the activation of unfolded protein response (UPR) pathway. This is consistent with its elevated expression in VRd (Bortezomib- Lenalidomide-Dexamethasone) non-responsive MM patients. PLUM localizes predominantly in the nucleus where it interacts directly with the disordered region of EZH2 (489-494 aa residues) to facilitate formation of the PRC2 complex and EZH2 activity. Disruption of this interaction using steric antisense oligonucleotides (ASOs) re-sensitized MMCLs to drug treatment in vitro and in vivo, correlating with the loss of EZH2 H3K27 trimethylation activity and PRC2 complex stability. Finally, we demonstrate that PLUM-EZH2 regulates the expression of tumour suppressor genes, FOXO3 and ZFP36, to activate the UPR pathway and promote chemoresistance in MM. These findings indicate that ncNF-κB pathway regulated lncRNA PLUM is oncogenic, acting through the PRC2/FOXO3/ZFP36 axis to confer chemoresistance in MM.
2025-06-23 | PXD054586 | Pride
Project description:In this study, multiomics profiling, including CUT&Tag, promoter capture Hi-C (PCHi-C), and microarray, identified LncRNA-ITGA2 as a novel elncRNA that was highly expressed in PDGF-induced proliferative human VSMCs. Notably, LncRNA-ITGA2 was significantly increased in both plasma and coronary atherosclerotic tissues of patients with coronary artery disease (CAD) compared with control subjects. Loss- and gain-of-function studies revealed that LncRNA-ITGA2 potently increased PDGF-induced VSMC proliferation and migration. Moreover, LncRNA-ITGA2 overexpression enhanced neointimal hyperplasia in vivo in a mouse carotid artery injury model, exhibiting its partial functional conservation. RNA-sequencing and CRISPR-Cas9 gene-editing technology revealed integrin α2 (ITGA2) as a downstream target of LncRNA-ITGA2 in VSMCs. Mechanistically, promoter-enhancer interactions were detected by PCHi-C at the ITGA2 locus after PDGF-BB treatment. Chromatin immunoprecipitation sequencing (ChIP-Seq) and chromatin isolation by RNA purification (ChIRP)-qPCR showed that LncRNA-ITGA2 directly bound to the Enhancer-ITGA2 and increased H3K27 acetylation in both the Enhancer-ITGA2 and Promoter-ITGA2. In addition, we demonstrated, by ChIRP-MS and RNA immunoprecipitation, that LncRNA-ITGA2 interacted with the DNA binding-protein NONO (non-pou domain containing octamer-binding protein), which also bound to the ITGA2 promoter, as verified by the ChIP-qPCR assay. Ultimately, the knockout cell lines of NONO, LncRNA-ITGA2, and its promoter confirmed the above regulatory mechanism.
2024-12-31 | GSE248192 | GEO