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| Status |
Public on Nov 10, 2025 |
| Title |
Regulation of ribosomal gene expression and senescence by a PML-mTOR-RONIN nuclear complex in triple-negative breast cancer [ChIP-seq_mTOR] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer that associates with poor prognosis and a high risk of relapse with limited treatment options. While the induction of senescence, a state of arrested cell growth, is generally achieved by available anticancer treatments, senescence can adversely promote tumorigenesis through an upheld augmented inflammatory state called senescence-associated secretory phenotype (SASP). Thus, the precise delineation of underlying regulatory mechanisms governing senescence is urgently needed. Herein, we investigated the beneficial anticancer senescence response elicited by silencing of the expression of the promyelocytic leukemia protein (PML) in TNBC, where it exerts an oncogenic role. Functional genomics studies implicated the downregulation of a specific set of ribosomal protein (RP) genes tied to poor clinical outcome. Re-introduction of RPL38 or RPL39L alone but not RPS14, a favorable outcome-associated RP, was sufficient to block the senescence phenotype induced by PML knockdown. RP gene regulation by PML was found to involve the assembly of a previously unrecognized PML-mTOR-RONIN transcriptional complex at their promoters. Furthermore, we show that RONIN levels are elevated in TNBC and that RONIN silencing can recapitulate the senescent phenotype of PML-deficient cells. This work offers new therapeutic insights for TNBC that involve senescence-inducing therapies or senolytics.
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| Overall design |
mTOR ChIP-seq experiments were performed on TNBC MDA-MB-231 cells with input controls as a reference for peak calling.
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| Contributor(s) |
Medkour Y, Vernier M, Dufour CR, Giguère V |
| Citation(s) |
41206371 |
| |
| Submission date |
Nov 28, 2024 |
| Last update date |
Nov 11, 2025 |
| Contact name |
Vincent Giguère |
| E-mail(s) |
vincent.giguere@mcgill.ca
|
| Phone |
514-398-5899
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| Organization name |
McGill University
|
| Department |
Goodman Cancer Centre
|
| Street address |
1160 Pine Ave West, McIntyre Bldg Room 710
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| City |
Montréal |
| State/province |
QC |
| ZIP/Postal code |
H3A 1A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE283109 |
Regulation of ribosomal gene expression and senescence by a PML-mTOR-RONIN nuclear complex in triple-negative breast cancer |
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| Relations |
| BioProject |
PRJNA1191872 |
