Study Reveals Significant Up-Regulation of Potentially Disease-Specific Long Noncoding RNAs in NMOSD

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In a recent study, investigators observed a substantial up-regulation of long noncoding RNAs among patients with neuromyelitis optica spectrum disorder in comparison with heathy individuals.

Mohammad Taheri, PhD, researcher in the Institute of Human Genetics at Jena University Hospital, in Germany

Mohammad Taheri, PhD

Recently published in Scientific Reports, findings showed significant up-regulation of long noncoding RNAs (lncRNAs), most notable MEG3,in patients with neuromyelitis optica spectrum disorder (NMOSD), when compared with healthy controls. These results suggest that lncRNAs influence the pathobiology and progression of the disease and may be considered as appropriate disease markers for NMOSD.1

In the study, experiments in the peripheral blood samples showed significant up-regulation of PANDAR, NEAT1, TUG1 and MEG3 lncRNAs in NMOSD cases (n = 42) vs controls (n = 49). The expressions of mentioned lncRNAs were also higher in both men (n = 10) and women (n = 32) patients with NMOSD compared with the matched controls (men, n = 9; women, n = 39). Notably, investigators did not observe a difference in the expression of any of lncRNAs between both the women and men patients.

Top Clinical Takeaways

  • The study suggests that MEG3, PANDAR, NEAT1, and TUG1 lncRNAs can serve as potential disease markers for NMOSD, with MEG3 exhibiting superior performance in differentiation.
  • Positive correlations between TUG1 and PANDAR, as well as TUG1 and MEG3, hint at potential associations with age and disease onset, providing avenues for further research into the pathogenic effects of NMOSD.
  • Assessing lncRNA expression in different blood cell sets is recommended for a comprehensive understanding of their role in NMOSD pathobiology, according to the investigators.

“Cumulatively, NEAT1, PANDAR, MEG3 and TUG1 lncRNAs can be considered as appropriate disease markers for NMOSD. For better assessment of the role of these lncRNAs in the pathobiology of NMOSD, we suggest assessment of their expression in different sets of blood cells, including peripheral blood mononuclear cells,” lead author Mohammad Taheri, PhD, researcher in the Institute of Human Genetics at Jena University Hospital, in Germany, and colleagues wrote.1

READ MORE: Revised Recommendations Published to Improve Diagnosis and Treatment in NMOSD

In this analysis, investigators assessed the expression of NEAT1, TUG1, MEG3 and PANDAR lncRNAs in blood samples of patients with NMOSD and matched controls. The patients included in the study were admitted to hospitals affiliated to Shahid Beheshti University of Medical Sciences, were anti-aquaporin-4 antibody positive, and did not receive immunosuppressive treatment during 1 month before sampling. Researchers extracted the total RNA from blood samples using RNJia extraction kit (Roje Technologies Company, Iran) and made cDNA using AddScript cDNA Synthesis Kit (ADDBIO, South Korea). The expression of lncRNAs was then determined using RealQ Plus 2× Master Mix (AMPLIQON, Denmark).

Authors detected the strongest correlations between TUG1 and PANDAR (correlation coefficient = 0.9) and between TUG1 and MEG3 (Correlation coefficient = 0.8) in NMOSD cases. In the patient subgroups, MEG3 had the most robust over-expression compared with the normal participants. In addition, MEG3 demonstrated what investigators considered an “ideal performance in the differentiation of NMOSD cases from healthy patients” (Sensitivity and specificity values = 100%). The other lncRNAs also could efficiently separate NMOSD cases from control participants (AUC values = 0.97, 0.89 and 0.88 for PANDAR, NEAT1 and TUG1, respectively).

TUG1 and PANDAR expression levels were positively correlated with age and age at onset. Thus, it is possible that expression levels of these 2 lncRNAs are affected by disease course and reflect the pathogenic effects of NMOSD,” Taheri et al wrote.1 “However, we could not detect any correlation between their expression and Expanded Disability Status Scale (EDSS) scores either at the initial phase of the disorder or at the point that blood samples were collected. On the other hand, NEAT1 expression level was negatively correlated with EDSS at the start point.”

REFERENCES
1. Taheri M, Sadeghi A, Gharebaghi A, et al. Significant up-regulation of lncRNAs in neuromyelitis optica spectrum disorder. Sci Rep. 2023;13(1):18692. Published 2023 Oct 31. doi:10.1038/s41598-023-45457-w
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