Expressions of several sets of microRNAs get perturbed when differentiated astrocytoma are exposed to NMOSD patient sera with different seropositivity – A functional analysis

Neuromyelitis Optica Spectrum Disorder (NMOSD), is a rare auto-immune demyelinating disorder of the Central Nervous System. A circulating auto-antibody (AQP4-IgG) against aquaporin-4 (AQP4) is found in more than 80% patients. Other auto-antibodies like the one against Myelin oligodendrocyte glycoprotein (MOG) have also been reported. There are very few reports that study the intracellular changes within the astrocytes post exposure to both the auto-antibodies present in patients’ serum. Here, we compared the expression profiles of microRNAs within differentiated glioblastoma cell lines and how they regulate the signaling pathways, after their exposure for different time-lengths to AQP4-IgG and MOG-IgG+ve sera respectively using Next Generation Sequencing. Our data revealed that five microRNAs, hsa-miR-3687, hsa-miR-663a, hsa-miR-4466, hsa-miR-222-5p, hsa-miR 100-3p were significantly downregulated in differentiated U87MG cells treated with MOG+ve samples whereas two microRNAs hsa-miR- 6824-3p and hsa-miR-490-3p were significantly up and downregulated respectively in cells treated with AQP+ve sera. Functional enrichment analysis revealed the predominance of MAPK, PI3K-Akt, and calcium signaling pathways. The mechanism and significance of these functions in the context of NMOSD will be discussed. Besides revealing the potential role of microRNAs in the progression of this rare auto-immune disorder, this study will also portray a complete intra-cellular picture of molecular interactions post exposure to auto antibodies.

Audience Take Away

• NMOSD is a rare disease and a little information is known about the molecular mechanism of AQP+ve Neuromyelitis Optica. There are very few reports that talk about the intracellular changes that take place within the astrocytes after their exposure to AQP4 auto- antibody
• Audience will learn about the microRNAs that play an essential role in the progression of the disease and how they regulate the important intracellular signaling pathways playing key role in astrocytic fate.
• What happens to astrocytes when they are exposed to MOG-IgG auto-antibody is a completely new area to explore. This is the first study that will reveal some information in this context.