Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE65491
PROVIDER: PRJNA236312 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Regulatory RNA Apela Is a Component of a Negative Feedback Loop Regulating p53-Mediated Apoptosis in Embryonic Stem Cells (II)
| PRJNA259654 | ENA
Project description:Regulatory RNA Apela Is a Component of a Negative Feedback Loop Regulating p53-Mediated Apoptosis in Embryonic Stem Cells (III)
| PRJNA263940 | ENA
Project description:The tumor suppressor protein p53 orchestrates cellular responses to stress by regulating the transcription of target genes involved in processes such as cell cycle control, DNA damage repair and apoptosis. The protein kinase DYRK1B, known to promote cancer cell survival and contribute to DNA damage repair, is overexpressed in various tumor types. Here, we demonstrate that expression of DYRK1B - but not its closely related paralog DYRK1A - is upregulated by cytostatic drugs (Actinomycin D, Doxorubicin) in multiple cancer cell lines. This induction required functional p53 and was mediated by p53-dependent activation of the transcription factor RFX7. Furthermore, we show that DYRK1B physically interacts with RFX7 and counteracts its activation by p53, thereby establishing a negative feedback loop that attenuates RFX7- dependent gene expression. This inhibitory effect of DYRK1B was strictly dependent on its catalytic activity and could be blocked by using small-molecule DYRK1 inhibitors. In conclusion, our study identifies DYRK1B as an indirect p53 target that suppresses p53- mediated activation of RFX7. These findings suggest that pharmacological inhibition of DYRK1B may represent a therapeutic strategy to enhance RFX7 tumor suppressor function.
2026-03-31 | PXD067752 | Pride
Project description:The tumor suppressor protein p53 orchestrates cellular responses to stress by regulating the transcription of target genes involved in processes such as cell cycle control, DNA damage repair and apoptosis. The protein kinase DYRK1B, known to promote cancer cell survival and contribute to DNA damage repair, is overexpressed in various tumor types. Here, we demonstrate that expression of DYRK1B - but not its closely related paralog DYRK1A - is upregulated by cytostatic drugs (Actinomycin D, Doxorubicin) in multiple cancer cell lines. This induction required functional p53 and was mediated by p53-dependent activation of the transcription factor RFX7. Furthermore, we show that DYRK1B physically interacts with RFX7 and counteracts its activation by p53, thereby establishing a negative feedback loop that attenuates RFX7- dependent gene expression. This inhibitory effect of DYRK1B was strictly dependent on its catalytic activity and could be blocked by using small-molecule DYRK1 inhibitors. In conclusion, our study identifies DYRK1B as an indirect p53 target that suppresses p53- mediated activation of RFX7. These findings suggest that pharmacological inhibition of DYRK1B may represent a therapeutic strategy to enhance RFX7 tumor suppressor function.
2026-04-14 | PXD067742 | Pride
Project description:MicroRNA (miRNA) expression profiling identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions compared with primary melanomas. miR-638 enhanced the tumourigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling of miR-638 and antagomir-transduced cells identified new candidate genes as miR-638 targets, the majority of which is involved in p53-mediated apoptosis regulation. miR-638 depletion stimulated expression of p53 and its downstream target genes and induced apoptosis and autophagy in melanoma cells. miR-638 promoter analysis revealed transcription factor associated protein 2-α (TFAP2A) as a direct negative regulator of miR-638. Further analyses provided strong evidence for a double negative regulatory feedback loop between miR-638 and TFAP2A. Taken together, miR-638 may support melanoma progression by suppressing p53-mediated apoptosis pathways and by targeting the transcriptional repressor TFAP2A.
2014-01-30 | GSE54492 | GEO
Project description:MicroRNA (miRNA) expression profiling identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions compared with primary melanomas. miR-638 enhanced the tumourigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling of miR-638 and antagomir-transduced cells identified new candidate genes as miR-638 targets, the majority of which is involved in p53-mediated apoptosis regulation. miR-638 depletion stimulated expression of p53 and its downstream target genes and induced apoptosis and autophagy in melanoma cells. miR-638 promoter analysis revealed transcription factor associated protein 2-α (TFAP2A) as a direct negative regulator of miR-638. Further analyses provided strong evidence for a double negative regulatory feedback loop between miR-638 and TFAP2A. Taken together, miR-638 may support melanoma progression by suppressing p53-mediated apoptosis pathways and by targeting the transcriptional repressor TFAP2A.
2014-01-30 | GSE54493 | GEO
Project description:MicroRNA (miRNA) expression profiling identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions compared with primary melanomas. miR-638 enhanced the tumourigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling of miR-638 and antagomir-transduced cells identified new candidate genes as miR-638 targets, the majority of which is involved in p53-mediated apoptosis regulation. miR-638 depletion stimulated expression of p53 and its downstream target genes and induced apoptosis and autophagy in melanoma cells. miR-638 promoter analysis revealed transcription factor associated protein 2-M-NM-1 (TFAP2A) as a direct negative regulator of miR-638. Further analyses provided strong evidence for a double negative regulatory feedback loop between miR-638 and TFAP2A. Taken together, miR-638 may support melanoma progression by suppressing p53-mediated apoptosis pathways and by targeting the transcriptional repressor TFAP2A. TaqManM-BM-. low-density arrays (TLDA; human microRNA Cards A v2.1 & B v2.0, Applied Biosystems, Darmstadt, Germany) were used for measuring the expression of 667 human miRNAs in primary melanomas (PM, n=8), lymph node metastases (LNM, n=9) or distant cutaneous metastases (DCM, n=10).
2014-01-30 | E-GEOD-54492 | biostudies-arrayexpress
Project description:MicroRNA (miRNA) expression profiling identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions compared with primary melanomas. miR-638 enhanced the tumourigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling of miR-638 and antagomir-transduced cells identified new candidate genes as miR-638 targets, the majority of which is involved in p53-mediated apoptosis regulation. miR-638 depletion stimulated expression of p53 and its downstream target genes and induced apoptosis and autophagy in melanoma cells. miR-638 promoter analysis revealed transcription factor associated protein 2-? (TFAP2A) as a direct negative regulator of miR-638. Further analyses provided strong evidence for a double negative regulatory feedback loop between miR-638 and TFAP2A. Taken together, miR-638 may support melanoma progression by suppressing p53-mediated apoptosis pathways and by targeting the transcriptional repressor TFAP2A. Whole genome cDNA microarray (Illumina Human HT-12 v4 Expression BeadChip Kit, San Diego, CA 92122 USA) analyses were performed in duplicates using RNA extracted from SK-Mel-147 cells transfected with a non-targeting control, miR-638 or antagomiR-638.
2014-01-30 | E-GEOD-54493 | 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 | GSE180944 | GEO