CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA717752 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14082870.fastq.gz | Fastqsanger.gz | |||
| SRR14082871.fastq.gz | Fastqsanger.gz | |||
| SRR14082872.fastq.gz | Fastqsanger.gz | |||
| SRR14082873.fastq.gz | Fastqsanger.gz | |||
| SRR14082874.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 5 |
Similar Datasets
Project description:The goal of this study is to use H3K4me3 signal to mark the promoter regions of the p73 gene. The p73 gene expresses TAp73 and DNp73 isoforms, which use two different promoters. H3K4me3 is generally associated with the promoter of a gene and, therefore, can be used to mark the promoters for TAp73 and DNp73.
2021-04-16 | GSE169716 | GEO
Project description:The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete. Here, we analyze genetic interactions between mutations of CBFB and other highly mutated genes in human breast cancer datasets and find that CBFB and TP53 mutations are mutually exclusive, suggesting a functional association between CBFB and p53. Integrated genomic studies reveal that TAp73 is a common transcriptional target of CBFB and p53. CBFB cooperates with p53 to maintain TAp73 expression, as either CBFB or p53 loss leads to TAp73 depletion. TAp73 re-expression abrogates the tumorigenic effect of CBFB deletion. Although TAp73 loss alone is insufficient for tumorigenesis, it enhances the tumorigenic effect of NOTCH3 overexpression, a downstream event of CBFB loss. Immunohistochemistry shows that p73 loss is coupled with higher proliferation in xenografts. Moreover, TAp73 loss-of-expression is a frequent event in human breast cancer tumors and cell lines. Together, our results significantly advance our understanding of the tumor suppressive functions of CBFB and reveal a mechanism underlying the communication between the two tumor suppressors CBFB and p53.
| S-EPMC8121313 | biostudies-literature
Project description:Cancer stem cells (CSCs) are resistant to conventional chemotherapy and are hence responsible for cancer relapse. Pluripotency is a characteristic of CSCs which allows them to rapidly proliferate while maintaining the ability to differentiate into various lineages. We found that TAp73, but not its homologue p53, is required for the pluripotency of CSCs. TAp73 knockdown (KD) decreased SOD1 levels, increased ROS production and disturbed metabolism which induced differentiation and abrogated pluripotency in CSCs. TAp73 related decrease in pluripotency is linked to increased autophagy and senescence in CSCs. Furthermore, TAp73 KD also decreased the levels of pluripotency factor Sox-2 within heterogeneous cancer cell lines. Interestingly, TAp73-deficient CSCs strongly lose tumorigenic potential in mice and tumors that did form had significantly lower levels of SOD1 and pluripotency marker Oct4. Our findings reveal a unique role of TAp73 in CSCs development that is important to consider while devising future therapeutic strategies against cancer.
2019-03-05 | PXD005407 | Pride
Project description:The aim of the experiment was to analyse the gene expression differences between MEFs containing TAp73 or without TAp73, at basal levels in normal culture conditions, and upon treatment with hypoxia (by incubation in 1% oxygen) for 4 or 8 hrs. The analysis indicate that absence of TAp73 leads to changes in multiple cellular and biological processes.
2014-10-11 | GSE62236 | GEO
Project description:The aim of the experiment was to analyse the gene expression differences between MEFs containing TAp73 or without TAp73, at basal levels in normal culture conditions, and upon treatment with hypoxia (by incubation in 1% oxygen) for 4 or 8 hrs. The analysis indicate that absence of TAp73 leads to changes in multiple cellular and biological processes. TAp73-/- and Tap73+/+ MEFs that were untreated, or treated with hypoxia (in 1% oxygen) for 4 and 8 hours were used for gene expression analysis
2014-10-11 | E-GEOD-62236 | biostudies-arrayexpress
Project description:AR cooperates with SMAD4 to maintain muscle homeostasis
| PRJNA771642 | ENA
Project description:Although being essential to respiratory and reproductive tracts multiciliogenesis, TAp73 is dispensable for multiciliogenesis in the ventricles. TAp73 KO is accompanied by dramatic changes in ciliogenic microRNAs miR34bc and miR449 family members, suggestin TAp73 functions partially thorugh posttranscriptional nodes in brain ciliogenesis.
2019-05-21 | GSE108385 | GEO
Project description:Hepatocyte dedifferentiation is a major source of hepatocellular carcinoma (HCC), but its mechanisms are unknown. We explored the p73 expression in HCC tumors and studied the effects of transcriptionally active p73 (TAp73) in HCC cells. Expression profiles of p73 and patient clinical data were collected from the Genomic Data Commons (GDC) data portal and the TSVdb database, respectively. Global gene expression profiles were determined by pan-genomic 54K microarrays. The Gene Set Enrichment Analysis was used to identify TAp73-regulated gene sets. The effects of TAp73 were analyzed in monolayer cell culture, 3D-tumoroid and xenograft models in zebrafish using western blot, flow cytometry, fluorescence imaging, real-time polymerase chain reaction (RT-PCR), immunohistochemistry and morphological examination. TAp73 was significantly upregulated in HCC, and its high expression indicated poor patient survival. The induced expression of TAp73 caused landscape expression changes including genes involved in growth signaling, cell cycle, stress response, immunity, metabolism and development. HCC cells overexpressing TAp73 had lost hepatocyte lineage biomarkers including ALB, CYP3A4, AFP, HNF4α. In contrast, TAp73 upregulated genes promoting cholangiocyte lineage such as YAP, JAG1 and ZO-1, accompanied with an increase in metastatic ability. Our findings strongly suggest that TAp73 is a major promoter of malignant dedifferentiation of HCC cells Hepatocellular carcinoma (HCC) is a highly complex and heterogeneous type of cancer. Hepatocyte dedifferentiation is one of the important steps in the development of HCC. However, its molecular mechanisms are not well known. In this study, we report that TAp73 which is the major transcriptionally active form of p73 is overexpressed in HCC. Mechanically, TAp73 suppresses the expression of the hepatocyte markers including CYP3A4, AFP, ALB, HNF4a, while increasing the expression of several cholangiocyte markers in HCC cell lines. In conclusion, this report reveals a pro-oncogenic role for TAp73 in liver cancer.
2021-03-10 | GSE162860 | GEO
Project description:It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. However, knockin mice expressing Cbfb-MYH11 (Cbfb+/MYH11) showed defects in primitive hematopoiesis not seen in Cbfb null (Cbfb-/-) embryos indicating that Cbfb-MYH11 has repression independent activities as well. To identify gene expression changes associated with this novel activity, we compared the gene expression profile in the blood cells of Cbfb+/MYH11 and Cbfb-/- embryonic day 12.5 (E12.5) embryos with that of their wildtype littermates. Cbfb-MYH11 chimeras were mated to C57/Bl6 females to generate Cbfb+/MYH11 (Cbfb+/MYH11) and Cbfb+/+ (WT) embryos. Cbfb+/- x Cbfb+/- matings were used to generate Cbfb+/+ (Cbfb+/+) and Cbfb-/- (Cbfb-/-) embryos. Blood from 8-10 E12.5 embryos of the same genotype was pooled, and RNA was isolated, labeled, and hybridized to Affymetrix Genechip mouse microarray (430 2.0) chips. 4 chips were used for both the Cbfb+/MYH11 and littermate control samples. 3 chips were used for the Cbfb-/- samples and littermate control samples.
2010-04-12 | E-GEOD-19194 | biostudies-arrayexpress
Project description:It is known that CBFB-MYH11, the fusion gene generated by inversion of chromosome 16 in human acute myeloid leukemia, is causative for oncogenic transformation. However, the mechanism by which CBFB-MYH11 initiates leukemogenesis is not clear. Previously published reports showed that CBFB-MYH11 dominantly inhibits RUNX1 and CBFB, and such inhibition has been suggested as the mechanism for leukemogenesis. However, knockin mice expressing Cbfb-MYH11 (Cbfb+/MYH11) showed defects in primitive hematopoiesis not seen in Cbfb null (Cbfb-/-) embryos indicating that Cbfb-MYH11 has repression independent activities as well. To identify gene expression changes associated with this novel activity, we compared the gene expression profile in the blood cells of Cbfb+/MYH11 and Cbfb-/- embryonic day 12.5 (E12.5) embryos with that of their wildtype littermates.
2010-03-31 | GSE19194 | GEO