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Published on: July 25, 2011
circNup188/miR-760-3p/Map3k8 axis regulates inflammation in cerebral ischemia
Hui Zhang1, Jian Deng1, Kangling Huang1
1Department of Neurology, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), No. 1017, Dongmen North Road, Shenzhen, 518020, Guangdong, China.
Insights
Circular RNAs like circNup188 regulate inflammation in cerebral ischemia by targeting miR-760-3p and activating the NF-κB pathway, offering a new therapeutic target for this condition.
Area of Science:
- Neuroscience
- Molecular Biology
- Inflammation Research
Background:
- Cerebral ischemia is a critical condition with high mortality and disability rates.
- Circular RNAs (circRNAs) are implicated in cerebral ischemia-associated inflammation and represent potential therapeutic targets.
- Understanding the molecular mechanisms underlying cerebral ischemia inflammation is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of the circNup188/miR-760-3p/Map3k8 axis in regulating inflammation during cerebral ischemia.
- To explore circNup188 as a potential therapeutic target for cerebral ischemia.
Main Methods:
- Utilized a previously established sequencing dataset to identify relevant signaling pathways and circRNAs.
- Established an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) cell model to mimic cerebral ischemia.
- Assessed cell viability, apoptosis, inflammatory cytokine levels (TNF-α, IL-1β, IL-6), circRNA and mRNA expression (qRT-PCR), and NF-κB pathway activation (Western blot).
Main Results:
- KEGG analysis identified MAPK and NF-kappaB signaling pathways as key inflammatory pathways.
- circNup188 was found to play a significant role in the OGD/R cell model, with its regulation affecting cell function.
- circNup188 was shown to sponge miR-760-3p, and miR-760-3p, in turn, regulated Map3k8 expression, activating the NF-κB pathway and contributing to inflammation in the OGD/R model.
Conclusions:
- circNup188 may upregulate Map3k8 expression by sponging miR-760-3p, subsequently activating the NF-κB pathway involved in cerebral ischemia.
- This circRNA-miRNA-mRNA interaction provides a novel molecular mechanism contributing to cerebral ischemia development.
- The circNup188/miR-760-3p/Map3k8 axis presents a promising new therapeutic target for cerebral ischemia treatment.
Introduction:
Cerebral ischemia is a serious acute disease with high mortality and disability rates. circRNAs are associated with cerebral ischemia inflammation and can be used as therapeutic targets. We aimed to investigate circNup188/miR-760-3p/Map3k8 role in inflammation during cerebral ischemia.
Methods:
According to the sequencing results of previously published, signaling pathways and circRNAs related to inflammation were screened and looped for verification. In vitro OGD/R cell model was constructed to detect OGD/R effects on PC12 cell viability, apoptosis, inflammatory cytokines TNF-α, IL-1β and IL-6. qRT-PCR assessed circRNAs, circNup188 bound miRNAs, and four mRNAs associated with inflammation and brain diseases expressions. p65 and IkB-α and their phosphorylated proteins in NF-κB pathway and Map3k8 expressions were assessed by Western blot.
Results:
KEGG analysis revealed MAPK and NF-kappaB signaling pathways played a vital role in it, and were classic inflammatory pathways. circNup188, circU2, and circCnot2 were verified to be the loop structure. circNup188 might play an essential role in OGD/R cell model. Regulating circNup188 expression could affect OGD/R cells function. In addition, miR-760-3p might play a vital role in OGD/R cell model. Moreover, circNup188 regulated cerebral ischemia by sponging miR-760-3p. miR-760-3p might be involved in inflammation in OGD/R cell model by regulating Map3k8 to activate the NF-κB pathway.
Conclusions:
circNup188 might up-regulate Map3k8 expression through sponging miR-760-3p and then activate NF-κB pathway, which was involved in cerebral ischemia development. This study provided a new target for cerebral ischemia treatment.
