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| Status |
Public on Jun 23, 2022 |
| Title |
LncRNA ICR regulates endothelium inflammation through feedback activation of NF-κB signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The responsive and abundant lncRNAs to pro-inflammatory factors in human ECs were screened and validated by RNA sequencing and qPCR. ICAM1-related non-coding RNA (ICR) was identified as the most potential candidate. In vivo data confirmed ICR was upregulated in atherosclerotic plaque. Knock down and overexpression experiments showed that ICR plays an essential role for EC adhesion and migration as well as for the expression of its adjacent ICAM1 gene. Mechanistically, we unexpectedly found in quiescent ECs, ICR regulates mRNA stabilization of ICAM1 through a RNA duplex formation mechanism while in activated ECs, ICR modulated ICAM1 transcription via a NF-κB-dependent manner. RNA-seq and PCR analysis demonstrated a vast number of pro-inflammatory genes downstream of NF-κB were regulated by ICR. Further, CHIP assay showed p65 directly binds to ICR promoter and facilitate the transcription. Interestingly, we found p65 phosphorylation and degradation was in turn regulated by ICR, forming a feedback activation of NF-κB signaling. Finally, we screened siRNA of mouse ICR and delivered the shRNA adenovirus by intravenous injection in a high fat diet induced ApoE-/- atherosclerosis model, it was found that both aortic root stenosis and plaque area could be markedly inhibited by suppressing ICR.
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| |
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| Overall design |
silenced ICR with or without TNF-α treatment performed RNA-seq in endothelial cells
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| |
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| Contributor(s) |
Ding S |
| Citation(s) |
35714558 |
| |
| Submission date |
Sep 21, 2021 |
| Last update date |
Jun 23, 2022 |
| Contact name |
shuangjin ding |
| E-mail(s) |
[email protected]
|
| Organization name |
Peking University
|
| Department |
College of Future Technology
|
| Street address |
No.5 YiHeYuan Road, Haidian District Beijing 100871, China
|
| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
| |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA764870 |
| SRA |
SRP338055 |
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