An RNA-seq study in Friedreich ataxia patients identified miR148a-3p as a putative prognostic biomarker of the disease.

ABSTRACT: Friedreich’s Ataxia (FRDA) is a life-threatening hereditary ataxia with an incidence of 1:50,000 individuals in the Caucasian population and only one therapeutic drug approved solely in the United States. FRDA is a multi-systemic neurodegenerative disease; cardiac abnormalities are one of the major complications and the predominant cause of premature death. The onset of FRDA typically occurs between the ages of 5 and 15. Given the complexity and heterogeneity of the clinical features and the variability of their onset, the identification of biomarkers able to evaluate disease progression and to monitor the efficacy of treatments is essential to facilitate decision making in clinical practice. We performed an RNA-seq study evaluating the expression level of circulating small non-coding RNAs (sncRNA) on PBMCs of FRDA patients and of healthy donors (CTRL). A hierarchical clustering algorithm (HCA) detected a sncRNAs signature able to distin-guish CTRL from the majority of FRDA patients. Among the differentially expressed sncRNA, microRNAs are the most relevant group. Hsa-miR-148a-3p resulted significantly upregulated in FRDA plasma samples (p<0.05). Noteworthy, hsa-miR-148a-3p increase was significant also when LOFA (late onset FRDA patients) group was compared with control group (p<0.05). Analysis of ROC curve combining the expression values of hsa-miR-148a-3p and hsa-miR-223-3p, previously identified by our group and confirmed in this study, revealed an AUC of 0.86 with 95% confidence interval 0.77 to 0.95 (p-value <0.001). An in silico prediction analysis of target genes of both miRNA, indicated IL6ST gene, an interesting marker of neuroinflammation in FRDA, as a common target gene.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243874 | GEO | 2024/06/03

REPOSITORIES: GEO