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Cross-Talking Pathways of Rapidly Accelerated Fibrosarcoma-1 (RAF-1) in Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) becomes one of the main global burden diseases with the aging population. This study was to investigate the potential molecular mechanisms of rapidly accelerated fibrosarcoma-1 (RAF-1) in AD through bioinformatics analysis. Differential gene expression analysis was performed in GSE132903 dataset. We used weight gene correlation network analysis (WGCNA) to evaluate the relations among co-expression modules and construct global regulatory network. Cross-talking pathways of RAF-1 in AD were identified by functional enrichment analysis. Totally, 2700 differentially expressed genes (DEGs) were selected between AD versus non-dementia control and RAF-1-high versus low group. Among them, DEGs in turquoise module strongly associated with AD and high expression of RAF-1 were enriched in vascular endothelial growth factor (VEGF), neurotrophin, mitogen-activated protein kinase (MAPK) signaling pathway, oxidative phosphorylation, GABAergic synapse, and axon guidance. Moreover, cross-talking pathways of RAF-1, including MAPK, VEGF, neurotrophin signaling pathways, and axon guidance, were identified by global regulatory network. The performance evaluation of AUC was 84.2%. The gene set enrichment analysis (GSEA) indicated that oxidative phosphorylation and synapse-related biological processes were enriched in RAF-1-high and AD group. Our findings strengthened the potential roles of high RAF-1 level in AD pathogenesis, which were mediated by MAPK, VEGF, neurotrophin signaling pathways, and axon guidance.

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Data Availability

The RNA expression data from GSE132903, GSE33000, and GSE18553 datasets are available freely at GEO repository (https://www.ncbi.nlm.nih.gov/geo).

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Funding

This work was supported by the Shenyang Science and Technology Planning Project (21-173-9-13) to Dr. Hong Hong.

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  1. Hong Hong and Lujiao Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Hong Hong, Lujiao Yu, Wenqiang Cong, Kexin Kang, Yazhu Gao, Qing Guan, Haiyan Zhang & Zhike Zhou

  2. Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, Shenyang, 110001, Liaoning, China

    Xin Meng

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  1. Hong Hong
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Contributions

HH and LJY contribute equally to this work. LJY, KXK, and ZKZ conceived and designed the study. ZKZ, WQC and HH collected data and conducted the analysis. LJY, QG, and YZG wrote the original draft. XM, HYZ, and ZKZ reviewed and edited the paper. All authors reviewed and approved the final manuscript.

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Correspondence to Zhike Zhou.

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Supplementary Information

Figure S1:

Expression difference of RAF-1 and ROC curve. The expression level of RAF-1 in AD and control in GSE33000 (A). Prediction evaluation of ROC analysis in GSE33000 (B). The expression level of RAF-1 in AD and control in GSE118553 (C). Prediction evaluation of ROC analysis in GSE118553 (D).

Figure S2:

Scatter diagram of module membership versus gene significance for AD

Tables S1:

Signature genes of the four pathways

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Hong, H., Yu, L., Cong, W. et al. Cross-Talking Pathways of Rapidly Accelerated Fibrosarcoma-1 (RAF-1) in Alzheimer’s Disease. Mol Neurobiol 61, 2798–2807 (2024). https://doi.org/10.1007/s12035-023-03765-2

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