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Series GSE166996 Query DataSets for GSE166996
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.
Overall design Paired end RNA sequencing of PASMC samples treated with control and EZH2 siRNA (four of each)
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
Organization name Janssen R&D LLC
Street address 1400 McKean Road
City Spring House
State/province Pennsylvania
ZIP/Postal code 19477
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM5090463 K1: PAH-PASMCs
GSM5090464 K2: PAH-PASMCs
GSM5090465 K3: PAH-PASMCs
BioProject PRJNA702549
SRA SRP306906

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE166996_RAW.tar 43.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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