Identification of m1A/m6A/m5C/m7G-related genes and clusters associated with neuropathic pain

RNA methylation modifications, including N1 methyladenosine (m1A), N6-methyladenosine (m6A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) methylation, have been increasingly implicated in nervous system disorders. The aim of this study was to explore key m1A/m6A/m5C/m7G-related genes in neuropathic pain (NP).

NP-related gene expression data were downloaded from a public database. Differentially expressed m1A/m6A/m5C/m7G-related genes between the NP and control samples were screened. Subsequently, the RNA methylation-related clusters of NP were identified. Differentially expressed genes (DEGs) between different clusters were identified; this was followed by functional enrichment, weighted gene co-expression network, and protein-protein interaction analyses. Moreover, m1A/m6A/m5C/m7G-related DEGs were validated in a rat NP model constructed using spinal nerve ligation surgery.

Six m1A/m6A/m5C/m7G-related DEGs were identified between NP and normal samples, namely, Fto, Mettl3, Nsun2, Ythdf3, Wdr4, and Eif4e. Based on these RNA methylation-related genes, two distinct NP clusters were identified. The DEGs between the clusters were involved in multiple pathways, such as the MAPK and FoxO signaling pathways. Among the DEGs, 12, including Txn1 and Rps3a, were identified as key genes. Furthermore, upregulation of Fto expression and downregulation of Mettl3, Nsun2, and Ythdf3 expression were observed in NP rats compared with those in control rats.

Our findings reveal that genes associated with RNA methylation modifications, including Fto, Mettl3, Nsun2, and Ythdf3, may be involved in NP progression. Additionally, two RNA methylation-related DEG clusters were identified, and key pathways, such as the MAPK and FoxO signaling pathways, may participate in NP progression.