Integrated Transcriptome Analysis Reveals Molecular Subtypes and ceRNA Networks in Multiple Sclerosis

Area of Science:

• Neuroimmunology
• Genomics
• Molecular Biology

Background:

• Multiple sclerosis (MS) is a chronic central nervous system (CNS) autoimmune disease.
• Understanding MS molecular subtypes and mechanisms is crucial for developing effective therapies.

Purpose of the Study:

• To identify distinct molecular subtypes of MS using transcriptome data.
• To characterize these subtypes and explore potential regulatory interactions involving circRNAs and miRNAs.

Main Methods:

• Transcriptome data from 215 MS patients were analyzed using ConsensusClusterPlus.
• Differential gene expression, variability, and ceRNA interactions (circRNAs, miRNAs) were assessed.

Main Results:

• Three molecular subtypes were identified: MS-FCRL1 (C1), MS-BTG1 (C2), and MS-RPL38 (C3).
• Subtype C3 showed enrichment in neurodegenerative pathways, heightened immune activity, and immune cell infiltration, indicating a potentially more severe disease.
• 18 differentially expressed circRNAs and 22 miRNAs were identified, with EEF1D and TUBA1A as hub targets in C3.

Conclusions:

• Distinct immune pathway activation across MS subtypes highlights gene expression's role in disease heterogeneity.
• A proposed circ_0045537/miR-196a-5p/TUBA1A axis in subtype C3 may modulate microtubule dynamics and exacerbate MS severity.