4.4 Article

Dysregulation of NF-κB-Associated lncRNAs in Multiple Sclerosis Patients

Journal

JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 71, Issue 1, Pages 80-88

Publisher

HUMANA PRESS INC
DOI: 10.1007/s12031-020-01628-2

Keywords

Multiple sclerosis; lncRNA; NF-kappa B; Autophagy

Funding

  1. Shahid Beheshti University of Medical Sciences

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The study analyzed the expression levels of specific lncRNAs and genes in the peripheral blood of MS patients and healthy controls, revealing the significant down-regulation of lncRNAs HNFIA-ASI and LINC00305 in the pathogenesis of MS.
Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of several complex disorders such as immune-related disorders. Multiple sclerosis (MS) as an inflammatory disorder of the central nervous system has been associated with aberrant expression of several lncRNAs. In the current study, we assessed expression of NF-kappa B-, autophagy-, and obesity-associated lncRNAs/genes and two inflammatory cytokines in the peripheral blood of MS patients and healthy controls. LNC-MKI67IP was down-regulated in total MS patients compared with total controls (P value < 0.0001). However, when comparing its expression in a gender-based manner, no significant difference was found between patients and controls. Expression of HNFIA-ASI was significantly lower in total MS patients and patients of both sexes when compared with the matched controls (P value < 0.0001; P value = 0.03; P value = 0.004, respectively). Expression of LINC00305 had a similar pattern to HNFIA-ASI (P value < 0.0001; P value = 0.005; P value < 0.0001, respectively). Expressions of other assessed NF-kappa B associated lncRNAs were not different between cases and controls. Expression of IL-1B was significantly lower in total MS patients compared with total controls (P value < 0.0001). Such decreased expression was detected in female patients compared with female controls as well (P value < 0.0001). Expression of IL-6 was not different between cases and controls. Expression of CEBPA was higher in total MS patients compared with controls (P value = 0.047). However, when dividing study participants into male and female subgroups, no significant difference was detected between cases and gender-matched controls. There were no significant difference in the expression of any assessed autophagy-associated lncRNAs between cases and controls. ATG5. CEBPA, HNFIA-ASI, IL-IB. LINC00305. and LNC-MKI67IP could differentiate disease status with diagnostic power values of 0.781, 0.582, 0.744, 0.76, 0.926, and 0.703, respectively. Expression levels of ADINR and CHAST were correlated with age of MS patients and disease duration, respectively (r = 0.33. P< 0.0001; r = 0.34, P< 0.0001, respectively). The present study highlighted the role of a number lncRNAs in the pathogenesis of MS and supported the previous data regarding aberrant expression of these transcripts in this immunerelated disorder.

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