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Identification of Anoikis-Related Genes in Spinal Cord Injury: Bioinformatics and Experimental Validation
Wen Yin1,2, Zhipeng Jiang1,2, Youwei Guo1,2
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People's Republic of China.
Abstract:
Spinal cord injury (SCI) is a serious disease without effective therapeutic strategies. To identify the potential treatments for SCI, it is extremely important to explore the underlying mechanism. Current studies demonstrate that anoikis might play an important role in SCI. In this study, we aimed to identify the key anoikis-related genes (ARGs) providing therapeutic targets for SCI. The mRNA expression matrix of GSE45006 was downloaded from the Gene Expression Omnibus (GEO) database, and the ARGs were downloaded from the Molecular Signatures Database (MSigDB database). Then, the potential differentially expressed ARGs were identified. Next, correlation analysis, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis were employed for the differentially expressed ARGs. Moreover, miRNA-gene networks were constructed by the hub ARGs. Finally, RNA expression of the top ten hub ARGs was validated in the SCI cell model and rat SCI model. A total of 27 common differentially expressed ARGs were identified at different time points (1, 3, 7, and 14 days) following SCI. The GO and KEGG enrichment analysis of these ARGs indicated several enriched terms related to proliferation, cell cycle, and apoptotic process. The PPI results revealed that most of the ARGs interacted with each other. Ten hub ARGs were further screened, and all the 10 genes were validated in the SCI cell model. In the rat model, only seven genes were validated eventually. We identified 27 differentially expressed ARGs of the SCI through bioinformatic analysis. Seven real hub ARGs (CCND1, FN1, IGF1, MYC, STAT3, TGFB1, and TP53) were identified eventually. These results may expand our understanding of SCI and contribute to the exploration of potential SCI targets.
Insights
This study identifies seven key anoikis-related genes (ARGs) as potential therapeutic targets for spinal cord injury (SCI). These findings offer new insights into SCI mechanisms and potential treatments.
Area of Science:
- Neuroscience
- Genetics
- Bioinformatics
Background:
- Spinal cord injury (SCI) lacks effective treatments, necessitating exploration of underlying mechanisms.
- Anoikis, a form of programmed cell death, is implicated in SCI pathogenesis.
- Identifying specific genes involved in anoikis is crucial for developing therapeutic strategies for SCI.
Purpose of the Study:
- To identify key anoikis-related genes (ARGs) that could serve as therapeutic targets for spinal cord injury (SCI).
- To explore the biological functions and pathways associated with differentially expressed ARGs in SCI.
- To validate potential therapeutic targets in both in vitro and in vivo SCI models.
Main Methods:
- Downloaded mRNA expression data (GSE45006) and ARGs (MSigDB).
- Identified differentially expressed ARGs, performed enrichment analyses (GO, KEGG), and constructed protein-protein interaction (PPI) networks.
- Validated hub ARGs in SCI cell and rat models.
Main Results:
- Identified 27 common differentially expressed ARGs in SCI at multiple time points.
- Enrichment analyses revealed ARGs involved in proliferation, cell cycle, and apoptosis.
- Seven hub ARGs (CCND1, FN1, IGF1, MYC, STAT3, TGFB1, TP53) were validated in SCI models.
Conclusions:
- Identified 27 differentially expressed ARGs in SCI using bioinformatic analysis.
- Seven hub ARGs (CCND1, FN1, IGF1, MYC, STAT3, TGFB1, TP53) show potential as therapeutic targets for SCI.
- These findings enhance the understanding of SCI mechanisms and contribute to the development of novel SCI therapies.
