LncRNA01103/FGF13 axis promotes the progression of bone cancer pain by remodeling ac4C modification

Abstract Bone cancer pain (BCP) significantly impacts patients' quality of life, yet its causes and mechanisms remain unclear. Long noncoding RNAs (lncRNAs) have gained attention for their regulatory role in disease processes. Through analysis and validating of acRIP-seq data from our previous study, we discovered that lncRNA01103 undergoes N4-acetylcytidine (ac4C) modification and increased expression in the SDH of BCP rats. Interestingly, ac4C modification influences the stability of lncRNA01103, impacting its expression levels. Further experiments revealed that lncRNA01103 is localized in SDH neurons and translocated towards the nucleus in BCP rats. Knockdown of lncRNA01103 reversed BCP, spinal c-fos neuron sensitization, and pain-related negative behaviors. Transcriptomic analysis identified FGF13 as a key target of lncRNA01103 in the neuronal nucleus, with FGF13 inhibition alleviating BCP and downregulating Nav1.7 sodium channel expression in SDH of BCP rats. Validation of lncRNA01103's role in regulating FGF13 expression and pain behaviors was confirmed through lncRNA01103-ASO sequence. This study highlights the role of NAT10/ac4C-mediated posttranscriptional modulation of lncRNA01103 in activating the FGF13-Nav1.7 signaling pathway and inducing hypersensitivity in BCP rats. Targeting the ac4C modification of lncRNA01103 could provide a novel therapeutic strategy for BCP.