Divergent lncRNA MYMLR regulates MYC by eliciting DNA looping and promoter-enhancer interaction
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE103085 | GEO | 2019/07/15
REPOSITORIES: GEO
Similar Datasets
Project description:Oncogenes can alter metabolism by changing the balance between anabolic and catabolic
processes. However, how oncogenes regulate tumor cell biomass remains poorly understood.
Using isogenic MCF10A cells transformed with nine different oncogenes, we show that specific
oncogenes reduce the biomass of cancer cells by promoting EV release. While MYC and
AURKB elicited the highest number of EVs, each oncogene selectively altered the protein
composition of released EVs. Likewise, oncogenes alter secreted miRNAs. MYC
overexpressing cells require ceramide, while AURKB require ESCRT to release high levels of
EVs. We identify an inverse relationship between MYC upregulation and activation of the
RAS/MEK/ERK signaling pathway for regulating EV release in some tumor cells. Finally,
lysosome genes and activity are downregulated in the context of MYC and AURKB, suggesting
that cellular contents instead of being degraded, were released via EVs. Thus, oncogene
mediated biomass regulation via differential EV release is a new metabolic phenotype.
2021-04-16 | MSV000087219 | MassIVE
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
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. Arrays: The total, cy3 labeled fraction and the cytoplasmic or nuclear, cy5 labeled fraction was hybridized on the same array. Data was imported and analyzed as a single color array. Expression of all known mRNAs and >10 000 lncRNAs was assessed in P493-6 B cells with low c-myc levels
2015-02-01 | E-GEOD-59478 | biostudies-arrayexpress
Project description:Recent evidence suggests that non-coding RNAs play an integral regulatory role in numerous functions in lung cancer development. Here, we report identification of a novel lncRNA, herein termed TP53-inhibiting lncRNA (TILR), which plays a role as a constitutive negative regulator of p53 expression and hence its functions including activation of downstream genes such as p21 and MDM2 and induction of apoptosis. Proteomic search for TILR-associated protein revealed the association with PCBP2, and the mid-portion of TILR was required for both PCBP2 and p53 mRNA binding. In addition, depletion of PCBP2 faithfully phenocopied effects of TILR silencing. We also found that TILR suppressed p53 expression post-transcriptionally as well as via a positive feedback loop between p53 and the Fanconi anemia pathway genes. Taken together, our findings clearly demonstrate that TILR constitutively inhibits p53 expression in cooperation with PCBP2, maintaining p53 transcriptional activity at a level sufficiently low for avoidance of spurious apoptosis induction.
2022-12-19 | GSE180940 | GEO
Project description:Recent evidence suggests that non-coding RNAs play an integral regulatory role in numerous functions in lung cancer development. Here, we report identification of a novel lncRNA, herein termed TP53-inhibiting lncRNA (TILR), which plays a role as a constitutive negative regulator of p53 expression and hence its functions including activation of downstream genes such as p21 and MDM2 and induction of apoptosis. Proteomic search for TILR-associated protein revealed the association with PCBP2, and the mid-portion of TILR was required for both PCBP2 and p53 mRNA binding. In addition, depletion of PCBP2 faithfully phenocopied effects of TILR silencing. We also found that TILR suppressed p53 expression post-transcriptionally as well as via a positive feedback loop between p53 and the Fanconi anemia pathway genes. Taken together, our findings clearly demonstrate that TILR constitutively inhibits p53 expression in cooperation with PCBP2, maintaining p53 transcriptional activity at a level sufficiently low for avoidance of spurious apoptosis induction.
2022-12-19 | GSE180944 | GEO
Project description:Despite the established role of the transcription factor MYC in cancer, little is known about the involvement of lncRNAs in mediating MYC’s function. Here we have intersected RNA-sequencing data from MYC-inducible cell lines, from a cohort of 91 mature B-cell lymphomas and from sorted germinal-center B-cells. By this approach, we identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated by MYC in the model cell lines. Among them we focused on a lncRNA that we named MINCR, showing a strong correlation with MYC expression in MYC-positive lymphomas and in pancreatic ductal adenocarcinomas. RNAi experiments showed that MINCR controls cellular viability by influencing the expression of MYC-regulated cell cycle genes. Finally we provide evidences that down-regulation of AURKA, AURKB and CTD1 may explain the reduction in cellular proliferation observed upon MINCR knock-down. We therefore suggest that MINCR acts as a modulator of MYC transcriptional control of cell cycle genes.
| EGAS00001001199 | EGA
Project description:Targeting “oncogene addiction” is a promising strategy for anti-cancer therapy. Here, we report a potent inhibition of crucial oncogenes by p53 upon reactivation with small molecule RITA in vitro and in vivo. RITA-activated p53 unleashes transcriptional repression of anti-apoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin, blocks Akt pathway on several levels and downregulates c-Myc, cyclin E and B-catenin. p53 ablates c-Myc expression via several mechanisms at transcriptional and posttranscriptional level. We show that transrepression of oncogenes correlated with higher level of p53 bound to chromatin-bound p53 than transactivation of pro-apoptotic targets. Inhibition of oncogenes by p53 reduces the cell’s ability to buffer pro-apoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression. Experiment Overall Design: Breast carcinoma cell-line MCF7 was treated with the small-molecule p53 activator RITA for 2h, 8h, 16h and 24h.
2009-05-15 | E-GEOD-13291 | 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.
2015-02-01 | GSE59479 | GEO
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