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| Status |
Public on Jun 21, 2024 |
| Title |
Hypoxia-ischemia-induced Ntoco promotes ferroptosis via the Hnrnpab-mediated NF κB/Lcn2 axis following traumatic brain injury in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Evidence supports the contribution of long non-coding RNAs (lncRNAs) and ferroptosis to traumatic brain injury (TBI) pathogenesis. However, lncRNA regulation in TBI-induced ferroptosis remains poorly understood. Herein, we identified an lncRNA, named noncoding transcript of chemokine (C-C motif) ligand 4 (Ccl4) overlapping (Ntoco), which was upregulated in TBI mice. The upregulation was initiated by hypoxia ischemia induced lower enrichment of H3K27me3 on the Ntoco promoter. Ntoco knockdown inhibited neuron ferroptosis, ameliorated spatial memory and lesion volume following TBI. Ntoco overexpression promoted neuron ferroptosis and recruited microglia to provoke an inflammatory response via Ccl4. Mechanistically, Ntoco facilitated K48-linked ubiquitination and protein degradation by binding to Hnrnpab, which suppressed NF-κB/Lcn2 signal axis activation, including decreased phosphorylation of IkBα, increased phosphorylation of IKKα/β, nuclear translocation of the NF-κB p65 subunit, and elevated Lcn2 expression. These data indicated that targeting Ntoco to mitigate ferroptosis might be a potential therapeutic strategy for TBI.
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| Overall design |
To further reveal the signaling pathways associated with Ntoco, we performed high-throughput transcriptome sequencing and KEGG pathway enrichment analysis of HT22 cells that knocked down and overexpressed Ntoco.
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| Contributor(s) |
Wang Q, Gao L |
| Citation missing |
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| Submission date |
Jun 21, 2023 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Linbo Gao |
| E-mail(s) |
gaolinbo@scu.edu.cn
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| Organization name |
Sichuan University
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| Street address |
No. 17, Section 3, Renmin South Road, Wuhou District
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| City |
Chengdu |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA986212 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235523_raw_FPKM.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
| GSE235523_raw_counts.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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