MicroRNAs (miRNAs), a class of non-coding RNAs, seem to play a key role in complexdiseases like multiple sclerosis (MS), as well as in many cognitive functions associated with the disease.In a previous cross-sectional evaluation on pediatric MS (PedMS) patients, the expression of somemiRNAs and their target genes were found to be associated with the scores of some neuropsychiatrictests, thus suggesting that they may be involved in early processes of cognitive impairment. To verifythese data, we asked the same patients to be re-evaluated after a 1-year interval; unfortunately, onlynine of them agreed to this further clinical and molecular analysis. The main results showed that 13dierentially expressed miRNAs discriminated the two time-points. Among them, the expressionof miR-182-5p, miR-320a-3p, miR-744-5p and miR-192-5p significantly correlated with the attentionand information processing speed performances, whereas the expression of miR-182-5p, miR-451a,miR-4742-3p and miR-320a-3p correlated with the expressive language performances. The analysis ofmRNA expression uncovered 58 predicted and/or validated miRNA-target pairs, including 23 targetgenes, some of them already associated with cognitive impairment, such as the transducing betalike 1 X-linked receptor-1 gene (TBL1XR1), correlated to disorders of neurodevelopment; the Snf2related CREBBP activator protein gene (SRCAP) that was found implicated in a rare form of dementia;and the glia maturation factor beta gene (GMFB), which has been reported to be implicated inneurodegeneration and neuroinflammation. No molecular pathways involving the most targetedgenes survived the adjustment for multiple data. Although preliminary, these findings showedthe feasibility of the methods also applied to longitudinal investigations, as well as the reliabilityof the obtained results. These findings should be confirmed in larger PedMS cohorts in order toidentify early markers of cognitive impairment, towards which more ecient therapeutic eorts canbe addressed.
A Pilot Longitudinal Evaluation of MicroRNAs for Monitoring the Cognitive Impairment in Pediatric Multiple Sclerosis
Nicoletta NuzzielloCo-primo
;Arianna ConsiglioCo-primo
;Flavio Licciulli;Sabino Liuni;Maria Liguori
Ultimo
Writing – Review & Editing
2020
Abstract
MicroRNAs (miRNAs), a class of non-coding RNAs, seem to play a key role in complexdiseases like multiple sclerosis (MS), as well as in many cognitive functions associated with the disease.In a previous cross-sectional evaluation on pediatric MS (PedMS) patients, the expression of somemiRNAs and their target genes were found to be associated with the scores of some neuropsychiatrictests, thus suggesting that they may be involved in early processes of cognitive impairment. To verifythese data, we asked the same patients to be re-evaluated after a 1-year interval; unfortunately, onlynine of them agreed to this further clinical and molecular analysis. The main results showed that 13dierentially expressed miRNAs discriminated the two time-points. Among them, the expressionof miR-182-5p, miR-320a-3p, miR-744-5p and miR-192-5p significantly correlated with the attentionand information processing speed performances, whereas the expression of miR-182-5p, miR-451a,miR-4742-3p and miR-320a-3p correlated with the expressive language performances. The analysis ofmRNA expression uncovered 58 predicted and/or validated miRNA-target pairs, including 23 targetgenes, some of them already associated with cognitive impairment, such as the transducing betalike 1 X-linked receptor-1 gene (TBL1XR1), correlated to disorders of neurodevelopment; the Snf2related CREBBP activator protein gene (SRCAP) that was found implicated in a rare form of dementia;and the glia maturation factor beta gene (GMFB), which has been reported to be implicated inneurodegeneration and neuroinflammation. No molecular pathways involving the most targetedgenes survived the adjustment for multiple data. Although preliminary, these findings showedthe feasibility of the methods also applied to longitudinal investigations, as well as the reliabilityof the obtained results. These findings should be confirmed in larger PedMS cohorts in order toidentify early markers of cognitive impairment, towards which more ecient therapeutic eorts canbe addressed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
