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Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage
Published on: July 3, 2014
Bioinformatics analysis identifies potential m6A hub genes in the pathogenesis of intracerebral hemorrhage
1Department of Neurosurgery, the First People's Hospital of Jiashan County, Jiaxing City, Zhejiang Province, PR China.
Insights
N6-methyladenosine (m6A) modifications are implicated in intracerebral hemorrhage (ICH) progression. The m6A gene YTHDF2 may drive ICH by increasing M1 macrophage infiltration or via a ceRNA network.
Area of Science:
- Biomedical research
- Molecular biology
- Stroke research
Background:
- Intracerebral hemorrhage (ICH) is a severe stroke type with high mortality and disability rates.
- The specific role of N6-methyladenosine (m6A) modifications in ICH pathogenesis is not well understood.
Purpose of the Study:
- To investigate the involvement of m6A regulatory genes in ICH.
- To identify key m6A genes and their potential mechanisms in ICH development.
Main Methods:
- Differential gene expression analysis to screen m6A-related differentially expressed genes (DEGs).
- Protein-protein interaction (PPI) networks to identify m6A hub genes.
- Correlation analyses with DNA methylation, receiver operating characteristic (ROC) curves for predictive ability, CIBERSORT algorithm for immune cell infiltration, and construction of competing endogenous RNA (ceRNA) networks.
Main Results:
- Twelve m6A regulatory enzymes were differentially expressed in ICH.
- Three m6A hub genes (YTHDF2, FTO, HNRNPA2B1) were identified.
- High YTHDF2 expression correlated with DNA hypomethylation, predicted ICH occurrence, and was associated with M1 macrophage infiltration.
- A ceRNA network involving YTHDF2 highlighted enrichment in transcriptional regulation and the LKB1 signaling pathway.
Conclusions:
- m6A modifications play a role in ICH progression.
- YTHDF2 emerges as a key m6A gene potentially regulating ICH through M1 macrophage infiltration or ceRNA pathways.
Background:
Intracerebral hemorrhage (ICH) is a type of stroke associated with a high rate of disability and mortality. The role of N6-methyladenosine (m6A) in ICH remains unclear.
Methods:
Screening of m6A DEGs by differentially expressed genes (DEGs) analysis. m6A hub genes in ICH were identified by protein-protein interaction (PPI) networks. Pearson correlation tests were used to explore the relationship between m6A hub genes and DNA methylation. m6A hub genes were examined by ROC curves for their ability to predict ICH occurrence. Immune cell infiltration and m6A hub gene correlation in ICH were analysed using the CIBERSORT algorithm. Construction of ceRNA networks and enrichment analysis by GO/KEGG.
Results:
A total of 12 m6A regulatory enzymes were differentially expressed after ICH. the PPI network screened three m6A hub genes, including YTHDF2, FTO and HNRNPA2B1. A high expression of YTHDF2 was associated with DNA hypomethylation after ICH and could better predict the development of ICH. yTHDF2 was associated with high infiltration of M1 macrophages after ICH. A ceRNA network was constructed based on the m6A central gene with target genes enriched in transcriptional regulation and the LKB1 signalling pathway.
Conclusion:
M6A modifications are involved in the progression of ICH. YTHDF2, an m6A key gene, may regulate ICH progression by promoting infiltration of M1 macrophages or through the ceRNA network.
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