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| Status |
Public on Apr 14, 2021 |
| Title |
Implication of EZH2 in the hyper-proliferative and apoptosis-resistant phenotype of pulmonary artery smooth muscle cells in PAH: a transcriptomic and proteomic approach |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The aim of this study was to determine whether EZH2 represents a new factor critically involved in the cancer-like phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and TCA cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.
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| |
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| Overall design |
Paired end RNA sequencing of PASMC samples treated with control and EZH2 siRNA (four of each)
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| |
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| Contributor(s) |
Krishna V, Jeyaseelan J, Boucherot O |
| Citation(s) |
33803922 |
| |
| Submission date |
Feb 17, 2021 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Vinod Krishna |
| E-mail(s) |
vkrish10@its.jnj.com
|
| Organization name |
Janssen R&D LLC
|
| Street address |
1400 McKean Road
|
| City |
Spring House |
| State/province |
Pennsylvania |
| ZIP/Postal code |
19477 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA702549 |
| SRA |
SRP306906 |
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