LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis
Background: At present, the treatment of intracerebral hemorrhage (ICH)-induced secondary brain injury (ISB) is limited, and the curative effect is not good. Long noncoding RNAs (lncRNAs) have been reported to play a role in ISB after ICH. We preliminarily monitored the induction effect of lncRNA-ps...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023022983 |
| _version_ | 1827957346627747840 |
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| author | Jia-xiang Chen Jian-wen Zhi Yi-ping Wang Bo Ning |
| author_facet | Jia-xiang Chen Jian-wen Zhi Yi-ping Wang Bo Ning |
| author_sort | Jia-xiang Chen |
| collection | DOAJ |
| description | Background: At present, the treatment of intracerebral hemorrhage (ICH)-induced secondary brain injury (ISB) is limited, and the curative effect is not good. Long noncoding RNAs (lncRNAs) have been reported to play a role in ISB after ICH. We preliminarily monitored the induction effect of lncRNA-pseudopodium-enriched atypical kinase 1 (PEAK1) on neuronal cell apoptosis after ICH through our previous study and further experimental verification. However, the specific role and mechanism of lncRNA-PEAK1 in neuronal cell apoptosis after ICH have not been reported. Methods: ICH cell models were established with hemin. Pro-inflammatory cytokines, cell proliferation, and apoptosis were evaluated by enzyme-linked immunosorbent assay, Cell Counting Kit-8 assay, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Moreover, lncRNA expression associated with apoptosis was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological functions of lncRNA-PEAK1, miR-466i-5p, and caspase8 were conducted in vitro. Further, we used bioinformatics, a dual-luciferase reporter assay, and rescue experiments to understand the mechanisms of competitive endogenous RNAs. Results: qRT-PCR revealed that lncRNA-PEAK1 was markedly upregulated in ICH cell models. LncRNA-PEAK1 knockdown decreased the interleukin-1β and tumor necrosis factor-alpha levels, promoted cell proliferation, weakened cell apoptosis, and downregulated the key molecular protein levels involved in the cell apoptosis pathway. Bioinformatics analysis and dual-luciferase reporter assay revealed that lncRNA bound to miR-466i-5p, and caspase 8 was a target of miR-466i-5p. The mechanistic analysis demonstrated that lncRNA-PEAK1/miR-466i-5p promoted neuronal cell apoptosis by activating the apoptosis pathway through caspase8 after ICH. Conclusion: Collectively, our investigation identified that the lncRNA-PEAK1/miR-446i-5p/caspase8 axis is closely related to neuronal cell apoptosis after ICH. Additionally, lncRNA-PEAK1 may be a potential target for ICH intervention. |
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| format | Article |
| id | doaj.art-cbef9ad2894e4331a6f16b250e3fa0ad |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T15:18:40Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
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| spelling | doaj.art-cbef9ad2894e4331a6f16b250e3fa0ad2023-04-29T14:55:15ZengElsevierHeliyon2405-84402023-04-0194e15091LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axisJia-xiang Chen0Jian-wen Zhi1Yi-ping Wang2Bo Ning3Department of Neurosurgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, Guangdong, China; Corresponding author.Background: At present, the treatment of intracerebral hemorrhage (ICH)-induced secondary brain injury (ISB) is limited, and the curative effect is not good. Long noncoding RNAs (lncRNAs) have been reported to play a role in ISB after ICH. We preliminarily monitored the induction effect of lncRNA-pseudopodium-enriched atypical kinase 1 (PEAK1) on neuronal cell apoptosis after ICH through our previous study and further experimental verification. However, the specific role and mechanism of lncRNA-PEAK1 in neuronal cell apoptosis after ICH have not been reported. Methods: ICH cell models were established with hemin. Pro-inflammatory cytokines, cell proliferation, and apoptosis were evaluated by enzyme-linked immunosorbent assay, Cell Counting Kit-8 assay, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Moreover, lncRNA expression associated with apoptosis was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological functions of lncRNA-PEAK1, miR-466i-5p, and caspase8 were conducted in vitro. Further, we used bioinformatics, a dual-luciferase reporter assay, and rescue experiments to understand the mechanisms of competitive endogenous RNAs. Results: qRT-PCR revealed that lncRNA-PEAK1 was markedly upregulated in ICH cell models. LncRNA-PEAK1 knockdown decreased the interleukin-1β and tumor necrosis factor-alpha levels, promoted cell proliferation, weakened cell apoptosis, and downregulated the key molecular protein levels involved in the cell apoptosis pathway. Bioinformatics analysis and dual-luciferase reporter assay revealed that lncRNA bound to miR-466i-5p, and caspase 8 was a target of miR-466i-5p. The mechanistic analysis demonstrated that lncRNA-PEAK1/miR-466i-5p promoted neuronal cell apoptosis by activating the apoptosis pathway through caspase8 after ICH. Conclusion: Collectively, our investigation identified that the lncRNA-PEAK1/miR-446i-5p/caspase8 axis is closely related to neuronal cell apoptosis after ICH. Additionally, lncRNA-PEAK1 may be a potential target for ICH intervention.http://www.sciencedirect.com/science/article/pii/S2405844023022983Intracerebral hemorrhageSecond brain injurylncRNAmiR-466i-5pCaspase 8Neuronal apoptosis |
| spellingShingle | Jia-xiang Chen Jian-wen Zhi Yi-ping Wang Bo Ning LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis Heliyon Intracerebral hemorrhage Second brain injury lncRNA miR-466i-5p Caspase 8 Neuronal apoptosis |
| title | LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis |
| title_full | LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis |
| title_fullStr | LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis |
| title_full_unstemmed | LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis |
| title_short | LncRNA-PEAK1 promotes neuronal apoptosis after intracerebral hemorrhage by miR-466i-5p/caspase 8 axis |
| title_sort | lncrna peak1 promotes neuronal apoptosis after intracerebral hemorrhage by mir 466i 5p caspase 8 axis |
| topic | Intracerebral hemorrhage Second brain injury lncRNA miR-466i-5p Caspase 8 Neuronal apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023022983 |
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