Similar Datasets
Project description:Acute myeloid leukemia (AML) is characterised by a series of genetic and epigenetic alterations that result in deregulation of transcriptional networks. One understudied source of transcriptional regulators are transposable elements (TEs), whose aberrant usage could contribute to oncogenic transcriptional circuits. However, the regulatory influence of TEs and their links to AML pathogenesis remain unexplored. Here we identify six endogenous retrovirus (ERV) families with AML-associated enhancer chromatin signatures that are enriched in binding of key regulators of hematopoiesis and AML pathogenesis. Using both locus-specific genetic editing and simultaneous epigenetic silencing of multiple ERVs, we demonstrate that ERV deregulation directly alters the expression of adjacent genes in AML. Strikingly, deletion or epigenetic silencing of an ERV-derived enhancer suppresses cell growth by inducing apoptosis in leukemia cell lines. This work reveals that ERVs are a previously unappreciated source of AML enhancers that may be exploited by cancer cells to help drive tumour heterogeneity and evolution.
| S-EPMC7360734 | biostudies-literature
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136763 | GEO
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136760 | GEO
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136759 | GEO
Project description:Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia
| PRJNA563616 | ENA
Project description:Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia [DNase-Seq]
| PRJNA563620 | ENA
Project description:Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia [ChIP-Seq]
| PRJNA563608 | ENA
Project description:Endogenous retroviruses are a source of oncogenic enhancers in acute myeloid leukemia [RNA-Seq]
| PRJNA563622 | ENA
Project description:IntroductionEmerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood.MethodsIn this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis.ResultsTwo HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis.DiscussionCollectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.
| S-EPMC10808309 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-05-30 | GSE247302 | GEO