Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA315254 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3239810.fastq.gz | Fastqsanger.gz | |||
| SRR3239811.fastq.gz | Fastqsanger.gz | |||
| SRR3239812.fastq.gz | Fastqsanger.gz | |||
| SRR3239814.fastq.gz | Fastqsanger.gz | |||
| SRR3239815.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large.
2022-09-07 | GSE212430 | GEO
Project description:Chromosomal translocations juxtaposing the androgen-responsive TMPRSS2 promoter with the ETS-family transcription factor ERG result in aberrant ERG up-regulation in approximately 50% of prostate cancers. Studies to date have demonstrated important roles of ERG in inducing oncogenic properties of prostate cancer. Its molecular mechanisms of action, however, are yet to be fully understood. To address these questions, we generated engineered LNCaP cells with ERG overexpression followed by LEF1 knockdown as well as control cell lines. To further investigate the role of LEF1 in ERG fusion positive samples, we also knockdown ERG in VCaP cell line. We performed microarray analysis on LNCaP cells with ERG overexpression followed by LEF1 knockdown using siRNA. We also knockdown endogenous ERG in fusion-positive cell line VCaP.
2013-05-29 | E-GEOD-47423 | biostudies-arrayexpress
Project description:Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
2023-05-02 | GSE217126 | GEO
Project description:Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
2023-05-01 | GSE125985 | GEO
Project description:Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
2023-05-01 | GSE125984 | GEO
Project description:Ewing sarcoma, a rare and aggressive pediatric cancer, is characterized by chromosomal translocations that give rise to chimeric transcription factors. The most frequent of these chromosomal translocations is the t(11;22) that produces the fusion of the EWSR1 and FLI1 genes to generate the chimeric transcription factor EWSR1::FLI1. EWSR1::FLI1 is the main oncogenic event in Ewing's sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels may fluctuate in Ewing sarcoma cells, giving rise to two cell populations: cells expressing low levels of EWSR1::FLI1 are characterized by a more migratory and invasive phenotype, while cells expressing high levels of EWSR1::FLI1 are more proliferative. The identification and functional characterization of EWSR1::FLI1 gene targets is therefore relevant to understanding the pathobiology of Ewing sarcoma, which in turn could contribute to the identification of new therapeutic targets. Using this approach, we have observed that CD44, a transmembrane protein involved in cell adhesion and migration and associated with metastasis in various cancer types, is overexpressed in the EWSR1::FLI1-low phenotype. Our results suggest that CD44 may play a role in regulating cell migration in Ewing sarcoma cells and thus contribute to the spread of tumor cells.
2023-07-25 | GSE232739 | GEO
Project description:Chromosomal translocations juxtaposing the androgen-responsive TMPRSS2 promoter with the ETS-family transcription factor ERG result in aberrant ERG up-regulation in approximately 50% of prostate cancers. Studies to date have demonstrated important roles of ERG in inducing oncogenic properties of prostate cancer. Its molecular mechanisms of action, however, are yet to be fully understood. To address these questions, we generated engineered LNCaP cells with ERG overexpression followed by LEF1 knockdown as well as control cell lines. To further investigate the role of LEF1 in ERG fusion positive samples, we also knockdown ERG in VCaP cell line.
2013-05-29 | GSE47423 | GEO
Project description:Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D). Single replicates of each cell line underwent ATAC-seq
2023-05-01 | GSE216874 | GEO
Project description:Large-scale chromosomal translocations are frequent oncogenic drivers in acute myeloid leukemia (AML). These translocations often occur in critical transcriptional/epigenetic regulators and contribute to malignant cell growth through alteration of normal gene expression. Despite this knowledge, the specific gene expression alterations that contribute to the development of leukemia remain incompletely understood. Here, through characterization of transcriptional regulation by the RUNX1-ETO fusion protein, we have identified Ras-association domain family member 2 (RASSF2) as a critical gene that is aberrantly transcriptionally repressed in t(8;21)-associated AML. Based on this, we performed molecular and functional characterization of RASSF2 in AML cells.
2019-11-27 | GSE141088 | GEO
Project description:For the largest class of human tumors, those of epithelial origin, little is known about their initiating genetic hits or cells of origin. Whether tissue stem cells or more committed progenitors are targets for transformation is also uncertain. Experience in hematopoietic malignancies and sarcomas teaches that recurrent chromosomal translocations represent initiating oncogenic events. To develop a system in which epithelial tumorigenesis can be assessed from the initial event to frank malignancy, we have generated mice that conditionally express the Etv6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of one form of human breast cancer. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed, bipotent or CD61+ luminal alveolar progenitors, can be targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through the AP1 complex. Our model supports the existence of an epithelial cell hierarchy in both normal mammary glands and malignancy. To our knowledge, this is the first murine model of human epithelial cancer based on a recurrent chromosomal translocation. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models. Experiment Overall Design: Reference X Sample
2008-06-16 | E-GEOD-9343 | biostudies-arrayexpress