Identification of Novel Human-Specific Long Non-Coding RNAs in Spinal Cord Astrocytoma Through RNA-Seq Analysis

Abstract Human spinal cord aging is associated with molecular changes that may affect neuronal function and tissue homeostasis, but the role of long non-coding RNAs (lncRNAs) in this process remains poorly understood. In this study, RNA-sequencing data from young and old human spinal cord samples were analyzed using an integrated bioinformatics pipeline, including transcript assembly, novel lncRNA identification, differential expression analysis, co-expression analysis, functional enrichment, evolutionary conservation, and SNP analysis. A total of 1,669 novel lncRNAs were identified, among which three transcripts (MSTRG.24062.6, MSTRG.35781.3, and MSTRG.57931.6) were significantly differentially expressed between the young and old age groups. Functional enrichment of co-expressed genes highlighted processes related to protein targeting to membrane, synaptic signaling, neuron projection organization, calcium ion transport, and membrane potential regulation. KEGG pathway analysis identified adrenergic signaling in cardiomyocytes as the most significantly enriched pathway. Conservation analysis revealed that all identified novel lncRNAs were human-specific and unmapped to the mouse genome. Genetic variant analysis identified 11,243 variants across 496 novel lncRNAs, with SNPs accounting for more than 95%. Transitions were more frequent than transversions, and variant distribution varied across chromosomes and lncRNAs. A weak positive correlation between SNP count and lncRNA expression suggested a limited association between genetic variation and expression levels. Overall, this study provides a comprehensive characterization of novel lncRNAs associated with human spinal cord aging and establishes a foundation for future studies investigations into their potential regulatory roles in age related molecular changes in spinal cord aging.