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| Status |
Public on Aug 26, 2024 |
| Title |
The loss of an orphan nuclear receptor NR2E3 augments Wnt/β-Catenin signaling via epigenetic dysregulation that promotes the Sp1-β catenin-p300 interactions in hepatocellular carcinoma. |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The orphan nuclear receptor NR2E3 (Nuclear receptor subfamily 2 group E, Member 3) is an epigenetic player essential for p53 activation during liver injuries through its modulation of chromatin accessibility. Nonetheless, a precise tumor suppressive and epigenetic role of NR2E3 in hepatocellular carcinoma (HCC) remains unclear. HCC patients expressing low NR2E3 exhibit unfavorable clinical outcomes, aligning with heightened activation of the WNT/β-catenin signaling pathway. The murine HCC models utilizing NR2E3 knockout mice consistently exhibits accelerated liver tumor formation and progression accompanied by enhanced activation of WNT/β-catenin signaling pathway and inactivation of p53 signaling pathway. At cellular level, the loss of NR2E3 increases the acquisition of aggressive cancer cell phenotype and tumorigenicity and upregulates key genes in the WNT/β-catenin pathway with enhanced chromatin accessibility. This event is mediated through increased formation of active transcription complex involving Sp1, β-catenin, and p300, a histone acetyltransferase, on the promoters of target genes. These findings demonstrate that the loss of NR2E3 promotes WNT/β-catenin signaling activation at cellular, organismal, and clinical levels. In summary, NR2E3 is a novel tumor suppressor that maintains epigenetic homeostasis, thereby preventing activation of WNT/β-catenin signaling that promotes HCC formation and progression.
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| Overall design |
Refer to individual Series
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| |
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| Citation(s) |
38790135 |
| |
| Submission date |
Sep 12, 2023 |
| Last update date |
Aug 27, 2024 |
| Contact name |
Kyounghyun Kim |
| E-mail(s) |
kkim@uams.edu
|
| Organization name |
University of Arkansas Medical Sciences
|
| Department |
Pharmacology & Toxicology
|
| Street address |
Rm 318 CI.3329 4104 Outpatient Circle
|
| City |
Little Rock |
| State/province |
AR |
| ZIP/Postal code |
72205 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (8)
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| This SuperSeries is composed of the following SubSeries: |
| GSE243017 |
The Loss of an orphan Nuclear Receptor augments Wnt/β-Catenin signaling via epigenetic dysregulation that promotes Sp1 and Myc interactions in Hepatocellular Carcinoma Development [RNA-seq] |
| GSE243019 |
The Loss of an orphan Nuclear Receptor augments Wnt/β-Catenin signaling via epigenetic dysregulation that promotes Sp1 and Myc interactions in Hepatocellular Carcinoma Development [FAIRE-seq] |
|
| Relations |
| BioProject |
PRJNA1015731 |
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