Widespread transposable element-driven oncogene expression in cancers
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113946 | GEO | 2019/02/05
REPOSITORIES: GEO
Similar Datasets
Project description:Widespread transposable element-driven oncogene expression in cancers
| PRJNA454575 | ENA
Project description:Cryptic promoters within transposable elements (TEs) are transcriptionally reactivated in tumors to create novel TE-gene chimeric transcripts, which can produce immunogenic antigens. We performed the most comprehensive screen to date for these TE exaptation events in 33 TCGA tumor types, 675 cancer cell lines, and 11,686 GTEx adult tissue transcriptomes and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Resultant whole lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on cancer cell surfaces. In addition, we highlight the tumor-specific membrane proteins transcribed from TE promoters that can expose novel epitopes on the extracellular surface of cancer cells. Here, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that can be therapeutically exploited through immunotherapy approaches.
2023-01-21 | PXD033351 | Pride
Project description: Not available
| S-EPMC6443099 | biostudies-literature
Project description:We charted the transcription start sites (TSSs) landscape globally to determine the expressed isoform of each gene and validate the precence of transposable element-derived transcript. Cryptic promoters within transposable elements (TEs) are transcriptionally reactivated in tumors to create novel TE-gene chimeric transcripts, which can produce immunogenic antigens. We performed the most comprehensive screen to date for these TE exaptation events in 33 TCGA tumortypes,675 cancer cell lines, and 11,686 GTEx adult tissue transcriptomes and identified 201,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Resultant whole lysate and HLA-pull down mass spectrometry data confirmed that TS-TEAs are presented on cancer cell surfaces. In addition, we highlight the tumor-specific membrane proteins transcribed from TE promoters that can expose novel epitopes on the extracellular surface of cancer cells. Here, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that can be therapeutically exploited through immunotherapy approaches.
2023-01-20 | GSE201021 | GEO
Project description: Not available
| S-EPMC4898795 | biostudies-literature
Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation. Examination of flower bud small RNAs from wild type and 5 single or double mutant combinations, many of which have biological replicates. In addition, IP purification of the AGO6 protein (and mock no-antigen controls) followed by sequencing of the incorporated small RNAs. Replicate A for Col and ddm1 are submitted in GSE41755
2014-11-14 | E-GEOD-57191 | biostudies-arrayexpress
Project description:The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis. Whole lenses were removed from 2, 14, and 42 day old Dbl transgenic and wild type mice. 4 to 8 individual lenses were pooled . Three independent pools from each time and condition were used as replicates.
2009-06-01 | E-GEOD-15694 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4133154 | biostudies-literature
Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation.
2014-11-14 | GSE57191 | GEO
Project description:The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation. We have generated transgenic mice introducing the onco-Dbl cDNA sequences linked to the metallothionein promoter into the germ line of FVB mice and found that onco-Dbl expression affected proliferation, migration and differentiation of lens epithelial cells. We used high density oligonucleotide microarray to define the transcriptional profile induced by Dbl in the lenses of transgenic mice and observed modulation of genes encoding proteins promoting epithelial-mesenchymal transition (EMT). Moreover, genes encoding proteins involved in the positive regulation of apoptosis were markedly down regulated while anti-apoptotic genes were strongly up-regulated. Finally, several genes encoding proteins involved in the process of angiogenesis were up-regulated. These observations were validated by histological and immunohistochemical examination of the transgenic lenses, where vascularization can be readily observed. Thus, onco-Dbl expression in mouse lenses induces disruption of the lens architecture, epithelial cell proliferation, EMT, evasion from cell death, and aberrant angiogenesis.
2009-06-01 | GSE15694 | GEO