LINC00641 Expression and a Predicted LINC00641-Associated RNA Network in Multiple Sclerosis

Abstract Background Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by demyelination and neurodegeneration. Long non-coding RNAs may contribute to gene-regulatory changes in MS, but the involvement of LINC00641 has not been investigated. Methods and Results LINC00641 expression was measured by quantitative real-time PCR in peripheral blood samples from 48 patients with MS and 48 healthy controls. LINC00641-associated mRNAs were retrieved from ENCORI and integrated with differential-expression analysis of the GSE137143 RNA-seq dataset. Protein-interaction analysis, functional enrichment, miRNA-target prediction, and receiver operating characteristic analyses were then performed. LINC00641 was significantly upregulated in MS and showed case-control discriminatory performance (AUC = 0.74). Six LINC00641-associated genes—DDX5, HNRNPC, THRAP3, YY1, SUPT16H, and HP1BP3—were significantly upregulated in the RNA-seq dataset, with individual AUC values of 0.64–0.71. A logistic-regression model combining the six genes showed an AUC of 0.806. Eleven predicted miRNAs were shared among the six genes, and enrichment analysis linked the gene set mainly to RNA splicing, mRNA processing, and chromatin organization. Conclusions LINC00641 is upregulated in MS, and integration of experimental expression data with transcriptomic and network analyses identifies a LINC00641-associated RNA signature linked to RNA-processing pathways. These findings support independent validation and functional investigation of LINC00641 and the associated network as candidate molecular biomarkers and regulators in MS.