Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA301997 | ENA |
REPOSITORIES: ENA
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Project description:Long noncoding RNAs (lncRNAs) have emerged as key components in multiple cellular processes, although their physiological and pathological functions are not fully understood. To identify cancer-related lncRNAs, we screened for those that are epigenetically silenced in colorectal cancer (CRC). Through a genome-wide analysis of histone modifications in CRC cells, we found that the transcription start sites (TSSs) of 1,027 lncRNA genes acquired trimethylation of histone H3 lysine 4 (H3K4me3) after DNA demethylation. Integrative analysis of chromatin signatures and the DNA methylome revealed that the promoter CpG islands (CGIs) of 66 lncRNA genes contained cancer-specific methylation. By validating the expression and methylation of lncRNA genes in CRC cells, we ultimately identified 20 lncRNAs, including ZNF582-AS1, as targets of epigenetic silencing in CRC. ZNF582-AS1 is frequently methylated in CRC cell lines (87.5%), primary CRCs (77.2%), colorectal adenomas (44.7%) and advanced adenomas (87.8%), suggesting that this methylation is an early event during colorectal tumorigenesis. Methylation of ZNF582-AS1 is associated with poor survival of CRC patients, and ectopic expression of ZNF582-AS1 suppressed colony formation by CRC cells. Our findings offer insight into the association between epigenetic alterations and lncRNA dysregulation in cancer and suggest that ZNF582-AS1 may be a novel tumor-suppressive lncRNA.
2015-11-13 | GSE74945 | GEO
Project description:Abnormal miRNA expression has been linked to the development and progression of human cancers, and such dysregulation can result from aberrant DNA methylation. We combined the analysis of miRNA expression data deposited with empirical DNA methylation data in HCT116 and DKO colon cancer cells (SRA accession# SRP001414) to identify novel DNA methylation regulated miRNAs. ABSTRACT: Abnormal microRNA (miRNA) expression has been linked to the development and progression of several human cancers, and such dysregulation can result from aberrant DNA methylation. While a small number of miRNAs is known to be regulated by DNA methylation, we postulated that such epigenetic regulation is more prevalent. By combining MBD-isolated Genome Sequencing (MiGS) to evaluate genome-wide DNA methylation patterns and microarray analysis to determine miRNA expression levels, we systematically searched for candidate miRNAs regulated by DNA methylation in colorectal cancer cell lines. We found 64 miRNAs to be robustly methylated in HCT116 cells and/or DNMT-1 and 3B doubleknock cells (DKO); eighteen of them were located in imprinting regions or already reported to be regulated by DNA methylation. In the remaining 46 miRNAs, expression levels of 18 were consistent with their DNA methylation status. Finally, 10 miRNAs were up-regulated by 5-aza-2'-deoxycytidine treatment and identified to be novel miRNAs regulated by DNA methylation. Moreover, we demonstrated the functional relevance of these epigenetically silenced miRNAs by ectopically expressing select candidates, which resulted in inhibition of growth and migration of cancer cells. Our study also provides a reliable strategy to identify DNA methylation-regulated miRNAs by combining DNA methylation profiles and expression data. [miRNA expression]: Total RNA was extracted from 3 biological replicate sets of HCT116 and DMNT-1 and 3B double knock out HCT116 (DKO) colorectal cancer cells.
2011-05-20 | E-GEOD-26819 | biostudies-arrayexpress
Project description:In mammals, many germline genes are repressed by epigenetic mechanisms to prevent their illegitimate expression in embryonic and somatic cells. To advance our understanding of the complete mechanisms restricting the expression of germline genes in mammals, we analyzed the chromatin signature of germline genes and performed a genome-wide CRISPR-Cas9 knock-out screen for genes involved in germline gene repression using a reporter system in which GFP is under the control of the epigenetically repressed Dazl germline promoter in mouse embryonic stem cells (ESCs). We showed that the repression of germline genes mainly depends on the polycomb complex PRC1.6 and DNA methylation, which function additively in mouse ESCs. Furthermore, we identified and validated several novel genes involved in the repression of germline genes, and characterized three of them: Usp7, Shfm1 (also known as Sem1) and Erh. Inactivation of Usp7, Shfm1 or Erh led to the upregulation of germline genes, as well as retrotransposons for Shfm1, in mouse ESCs. Functionally, Usp7 acts at two levels: firstly it associates with PRC1.6 components and represses germline genes independently of DNA methylation, and secondly it facilitates DNA methylation deposition at germline genes for long term repression. In summary, our study provides a global view of the epigenetic mechanisms and novel factors required for silencing germline genes in embryonic cells.
2023-02-03 | PXD030666 | Pride
Project description:Methylation-silenced genes in colorectal cancer cell lines
| PRJNA99441 | ENA
Project description:To screen for epigenetically silenced miRNAs, wecarried out miRNA microarray analysis in three colorectal cancer (CRC) cell lines (HCT116, DLD-1 and RKO) treated with or without 5-aza-2'-deoxycytidine (aza). HCT116 and RKO cells were also treated with aza plus 4-phenylbutyric acid (PBA). In addition, we analyzed HCT116 cells in which the DNA methyltransferase genes DNMT1 and DNMT3B were genetically disrupted (double knockout; DKO cells), thereby abrogating DNA methylation. Expression of a majority of miRNAs was downregulated in all three CRC cell lines tested, as compared to normal colonic mucosa. DAC treatment upregulated expression of a large number of miRNAs in all three CRC cell lines, and combination treatment with DAC plus PBA induced even greater numbers of miRNAs in CRC cells. The most profound effect on the miRNA expression profile was induced by genetic disruption of DNMT1 and DNMT3B in HCT116 cells.
2011-07-01 | GSE29900 | GEO
Project description:Abnormal miRNA expression has been linked to the development and progression of human cancers, and such dysregulation can result from aberrant DNA methylation. We combined the analysis of miRNA expression data deposited with empirical DNA methylation data in HCT116 and DKO colon cancer cells (SRA accession# SRP001414) to identify novel DNA methylation regulated miRNAs. ABSTRACT: Abnormal microRNA (miRNA) expression has been linked to the development and progression of several human cancers, and such dysregulation can result from aberrant DNA methylation. While a small number of miRNAs is known to be regulated by DNA methylation, we postulated that such epigenetic regulation is more prevalent. By combining MBD-isolated Genome Sequencing (MiGS) to evaluate genome-wide DNA methylation patterns and microarray analysis to determine miRNA expression levels, we systematically searched for candidate miRNAs regulated by DNA methylation in colorectal cancer cell lines. We found 64 miRNAs to be robustly methylated in HCT116 cells and/or DNMT-1 and 3B doubleknock cells (DKO); eighteen of them were located in imprinting regions or already reported to be regulated by DNA methylation. In the remaining 46 miRNAs, expression levels of 18 were consistent with their DNA methylation status. Finally, 10 miRNAs were up-regulated by 5-aza-2'-deoxycytidine treatment and identified to be novel miRNAs regulated by DNA methylation. Moreover, we demonstrated the functional relevance of these epigenetically silenced miRNAs by ectopically expressing select candidates, which resulted in inhibition of growth and migration of cancer cells. Our study also provides a reliable strategy to identify DNA methylation-regulated miRNAs by combining DNA methylation profiles and expression data.
2011-05-20 | GSE26819 | GEO
Project description:To screen for epigenetically silenced miRNAs, wecarried out miRNA microarray analysis in three colorectal cancer (CRC) cell lines (HCT116, DLD-1 and RKO) treated with or without 5-aza-2'-deoxycytidine (aza). HCT116 and RKO cells were also treated with aza plus 4-phenylbutyric acid (PBA). In addition, we analyzed HCT116 cells in which the DNA methyltransferase genes DNMT1 and DNMT3B were genetically disrupted (double knockout; DKO cells), thereby abrogating DNA methylation. Expression of a majority of miRNAs was downregulated in all three CRC cell lines tested, as compared to normal colonic mucosa. DAC treatment upregulated expression of a large number of miRNAs in all three CRC cell lines, and combination treatment with DAC plus PBA induced even greater numbers of miRNAs in CRC cells. The most profound effect on the miRNA expression profile was induced by genetic disruption of DNMT1 and DNMT3B in HCT116 cells. CRC cells were treated with 5-aza-2’-deoxycytidine (aza) or aza plus 4-phenylbutyrate (PBA). Nomal colon RNA was purchased from BioChain. Expression of 470 miRNAs was analyzed using Human miRNA Microarray V1 (G4470A; Agilent technologies, Santa Clara, CA, USA).
2011-07-01 | E-GEOD-29900 | biostudies-arrayexpress
Project description:UHRF1 is a major regulator of epigenetic mechanism and is overexpressed in various human malignancies. In this study, we examined the involvement of UHRF1 in aberrant DNA methylation in colorectal cancer (CRC). In CRC cells, transient UHRF1 knockdown rapidly induced DNA demethylation across entire genomic regions, including CpG islands, gene bodies and repetitive elements. Nonetheless, UHRF1 depletion only minimally reversed CpG island hypermethylation-associated gene silencing. However, the combination of UHRF1 depletion and histone deacetylase (HDAC) inhibition synergistically reactivated the silenced genes and strongly suppressed CRC cell proliferation. Our results suggest that (i) maintenance of DNA methylation in CRC cells is highly dependent on UHRF1; (ii) UHRF1 depletion rapidly induces DNA demethylation, though it is insufficient to fully reactivate the silenced genes; and (iii) dual targeting of UHRF1 and HDAC may be an effective new therapeutic strategy.
2019-05-21 | GSE106438 | GEO
Project description:UHRF1 is a major regulator of epigenetic mechanism and is overexpressed in various human malignancies. In this study, we examined the involvement of UHRF1 in aberrant DNA methylation in colorectal cancer (CRC). In CRC cells, transient UHRF1 knockdown rapidly induced DNA demethylation across entire genomic regions, including CpG islands, gene bodies and repetitive elements. Nonetheless, UHRF1 depletion only minimally reversed CpG island hypermethylation-associated gene silencing. However, the combination of UHRF1 depletion and histone deacetylase (HDAC) inhibition synergistically reactivated the silenced genes and strongly suppressed CRC cell proliferation. Our results suggest that (i) maintenance of DNA methylation in CRC cells is highly dependent on UHRF1; (ii) UHRF1 depletion rapidly induces DNA demethylation, though it is insufficient to fully reactivate the silenced genes; and (iii) dual targeting of UHRF1 and HDAC may be an effective new therapeutic strategy.
2019-05-21 | GSE106437 | GEO
Project description:UHRF1 is a major regulator of epigenetic mechanism and is overexpressed in various human malignancies. In this study, we examined the involvement of UHRF1 in aberrant DNA methylation in colorectal cancer (CRC). In CRC cells, transient UHRF1 knockdown rapidly induced DNA demethylation across entire genomic regions, including CpG islands, gene bodies and repetitive elements. Nonetheless, UHRF1 depletion only minimally reversed CpG island hypermethylation-associated gene silencing. However, the combination of UHRF1 depletion and histone deacetylase (HDAC) inhibition synergistically reactivated the silenced genes and strongly suppressed CRC cell proliferation. Our results suggest that (i) maintenance of DNA methylation in CRC cells is highly dependent on UHRF1; (ii) UHRF1 depletion rapidly induces DNA demethylation, though it is insufficient to fully reactivate the silenced genes; and (iii) dual targeting of UHRF1 and HDAC may be an effective new therapeutic strategy.
2019-05-21 | GSE113664 | GEO