Similar Datasets
Project description:The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers.Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR.
| S-EPMC5993051 | biostudies-literature
Project description:MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.
| PRJNA492293 | ENA
Project description:Myc is a well known transcription factor with important roles in cell cycle, apoptosis and cellular transformation. Long non-coding (lnc)RNAs have recently emerged as a important class of regulatory RNAs. Here, we show that lncRNAs are an extensive component of the Myc-regulated transcriptional program. Using the P493-6 inducible Myc model we demonstrate that both Myc-induced mRNAs and lncRNAs were significant enriched for Myc binding sites. In contrast to Myc-repressed mRNAs, Myc-repressed lncRNAs were significantly enriched for Myc binding sites. Subcellular localization analysis revealed that Myc-repressed lncRNAs and mRNAs are enriched in the nucleus while Myc-induced lncRNAs and mRNAs are enriched both in the cytoplasm and nucleus. Parallel analysis of differentially expressed lncRNAs and mRNAs identified 105 lncRNA-mRNA pairs that were in close vicinity, indicative for regulation in cis. To support the potential relevance of the Myc-regulated lncRNAs in cellular transformation, we analyzed their expression in primary Myc-high and Myc-low B-cell lymphomas. In total, 54% of the lncRNAs differentially expressed between the lymphoma subsets were identified as Myc-regulated in P493-6 cells. This study is the first to show that lncRNAs are an important factor within the Myc-regulated transcriptional program and indicates a marked difference between Myc-repressed lncRNAs and mRNAs. P493-6: 72h Tet treated (low c-myc levels), t=4h (intermediate c-myc levels), t=24h (high c-myc levels), untreated (steady state c-myc levels) Expression of all known mRNAs and >10 000 lncRNAs was assessed in P493-6 B cells with different c-myc levels
2015-02-01 | E-GEOD-59477 | biostudies-arrayexpress
Project description:Myc is a well known transcription factor with important roles in cell cycle, apoptosis and cellular transformation. Long non-coding (lnc)RNAs have recently emerged as a important class of regulatory RNAs. Here, we show that lncRNAs are an extensive component of the Myc-regulated transcriptional program. Using the P493-6 inducible Myc model we demonstrate that both Myc-induced mRNAs and lncRNAs were significant enriched for Myc binding sites. In contrast to Myc-repressed mRNAs, Myc-repressed lncRNAs were significantly enriched for Myc binding sites. Subcellular localization analysis revealed that Myc-repressed lncRNAs and mRNAs are enriched in the nucleus while Myc-induced lncRNAs and mRNAs are enriched both in the cytoplasm and nucleus. Parallel analysis of differentially expressed lncRNAs and mRNAs identified 105 lncRNA-mRNA pairs that were in close vicinity, indicative for regulation in cis. To support the potential relevance of the Myc-regulated lncRNAs in cellular transformation, we analyzed their expression in primary Myc-high and Myc-low B-cell lymphomas. In total, 54% of the lncRNAs differentially expressed between the lymphoma subsets were identified as Myc-regulated in P493-6 cells. This study is the first to show that lncRNAs are an important factor within the Myc-regulated transcriptional program and indicates a marked difference between Myc-repressed lncRNAs and mRNAs. P493-6: 72h Tet treated (low c-myc levels), t=4h (intermediate c-myc levels), t=24h (high c-myc levels), untreated (steady state c-myc levels)
2015-02-01 | GSE59477 | GEO
Project description:Characterisation of the impact of 24 hours of NMT inhibition (100 nM IMP1088) on the P493-6 cell line with medium levels of MYC and high levels of MYC.
2022-06-30 | GSE154336 | GEO
Project description:P493-6 cells are immortalized human peripheral B cells that carry a conditional, tetracycline-regulated myc gene. We present ChIP-seq analysis of key transcritional regulators in P493-6 cells expressing various levels of c-Myc: 0hr (low c-Myc levels), 1hr (intermediate c-Myc levels), 24hr (very high c-Myc levels) and No Tet (steady-state c-Myc levels). Brd4, c-Myc, Max, Med1, RNAPII, and the chromatin modification H3K27Ac were profiled in P493-6 cells
2012-11-14 | E-GEOD-42262 | biostudies-arrayexpress
Project description:P493-6 cells are immortalized human peripheral B cells that carry a conditional, tetracycline-regulated myc gene. We present ChIP-seq analysis of key transcritional regulators in P493-6 cells expressing various levels of c-Myc: 0hr (low c-Myc levels), 1hr (intermediate c-Myc levels), 24hr (very high c-Myc levels) and No Tet (steady-state c-Myc levels).
2012-11-14 | GSE42262 | GEO
Project description:Ectopic Myc Expression in P493-6 B-cells at three levels: High Myc, Low Myc and No Myc
2010-02-25 | GSE19703 | GEO
Project description:Ectopic Myc Expression in P493-6 B-cells at three levels: High Myc, Low Myc and No Myc High Myc, Low Myc and No Myc expressions
2010-03-09 | E-GEOD-19703 | biostudies-arrayexpress
Project description:Myc is a well known transcription factor with important roles in cell cycle, apoptosis and cellular transformation. Long non-coding (lnc)RNAs have recently emerged as a important class of regulatory RNAs. Here, we show that lncRNAs are an extensive component of the Myc-regulated transcriptional program. Using the P493-6 inducible Myc model we demonstrate that both Myc-induced mRNAs and lncRNAs were significant enriched for Myc binding sites. In contrast to Myc-repressed mRNAs, Myc-repressed lncRNAs were significantly enriched for Myc binding sites. Subcellular localization analysis revealed that Myc-repressed lncRNAs and mRNAs are enriched in the nucleus while Myc-induced lncRNAs and mRNAs are enriched both in the cytoplasm and nucleus. Parallel analysis of differentially expressed lncRNAs and mRNAs identified 105 lncRNA-mRNA pairs that were in close vicinity, indicative for regulation in cis. To support the potential relevance of the Myc-regulated lncRNAs in cellular transformation, we analyzed their expression in primary Myc-high and Myc-low B-cell lymphomas. In total, 54% of the lncRNAs differentially expressed between the lymphoma subsets were identified as Myc-regulated in P493-6 cells. This study is the first to show that lncRNAs are an important factor within the Myc-regulated transcriptional program and indicates a marked difference between Myc-repressed lncRNAs and mRNAs. Expression of all known mRNAs and >10 000 lncRNAs was assessed in primary lymphoma tissue with high c-myc levels (Burkitt lymphoma; BL) and low c-myc levels (chronic lymphocytic leukemia; CLL)
2015-02-01 | E-GEOD-59479 | biostudies-arrayexpress