friedreich ataxia (FRDA) is a life-threatening hereditary ataxia; its incidence is 1:50,000 individuals in the caucasian population. a unique therapeutic drug for FRDA, the antioxidant omaveloxolone, has been recently approved by the US food and drug administration (FDA). FRDA is a multi-systemic neurodegenerative disease; in addition to a progressive neurodegeneration, FRDA is characterized by hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. cardiomyopathy is 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 clinical features and the variability of their onset, the identification of biomarkers capable of assessing disease progression and monitoring the efficacy of treatments is essential to facilitate decision making in clinical practice. we conducted an RNA-seq analysis in peripheral blood mononuclear cells from FRDA patients and healthy donors, identifying a signature of small non-coding RNAs (sncRNAs) capable of distinguishing healthy individuals from the majority of FRDA patients. among the differentially expressed sncRNAs, microRNAs are a class of small non-coding endogenous RNAs that regulate posttranscriptional silencing of target genes. In FRDA plasma samples, hsa-miR-148a-3p resulted significantly upregulated. the analysis of the receiver operating characteristic (ROC) curve, combining the circulating expression levels of hsa-miR-148a-3p and hsa-miR-223-3p (previously identified by our group), revealed an area under the curve (AUC) of 0.86 (95%, confidence Interval 0.77-0.95; p-value < 0.0001). an in silico prediction analysis indicated that the IL6ST gene, an interesting marker of neuroinflammation in FRDA, is a common target gene of both miRNAs. our findings support the evaluation of combined expression levels of different circulating miRNAs as potent epi-biomarkers in FRDA. moreover, we found hsa-miR-148a-3p significantly over-expressed in Intermediate and late-onset friedreich ataxia patients' group (IOG and LOG, respectively) compared to healthy individuals, indicating it as a putative prognostic biomarker in this pathology.

Vancheri, C., Quatrana, A., Morini, E., Mariotti, C., Mongelli, A., Fichera, M., et al. (2024). An RNA-seq study in Friedreich ataxia patients identified hsa-miR-148a-3p as a putative prognostic biomarker of the disease. HUMAN GENOMICS, 18(1) [10.1186/s40246-024-00602-y].

An RNA-seq study in Friedreich ataxia patients identified hsa-miR-148a-3p as a putative prognostic biomarker of the disease

Vancheri, Chiara
Validation
;
Quatrana, Andrea
Methodology
;
Morini, Elena
Methodology
;
Rufini, Alessandra
Writing – Review & Editing
;
Condò, Ivano
Writing – Review & Editing
;
Testi, Roberto
Writing – Review & Editing
;
Novelli, Giuseppe
Funding Acquisition
;
Malisan, Florence
Supervision
;
Amati, Francesca
Supervision
2024-05-22

Abstract

friedreich ataxia (FRDA) is a life-threatening hereditary ataxia; its incidence is 1:50,000 individuals in the caucasian population. a unique therapeutic drug for FRDA, the antioxidant omaveloxolone, has been recently approved by the US food and drug administration (FDA). FRDA is a multi-systemic neurodegenerative disease; in addition to a progressive neurodegeneration, FRDA is characterized by hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. cardiomyopathy is 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 clinical features and the variability of their onset, the identification of biomarkers capable of assessing disease progression and monitoring the efficacy of treatments is essential to facilitate decision making in clinical practice. we conducted an RNA-seq analysis in peripheral blood mononuclear cells from FRDA patients and healthy donors, identifying a signature of small non-coding RNAs (sncRNAs) capable of distinguishing healthy individuals from the majority of FRDA patients. among the differentially expressed sncRNAs, microRNAs are a class of small non-coding endogenous RNAs that regulate posttranscriptional silencing of target genes. In FRDA plasma samples, hsa-miR-148a-3p resulted significantly upregulated. the analysis of the receiver operating characteristic (ROC) curve, combining the circulating expression levels of hsa-miR-148a-3p and hsa-miR-223-3p (previously identified by our group), revealed an area under the curve (AUC) of 0.86 (95%, confidence Interval 0.77-0.95; p-value < 0.0001). an in silico prediction analysis indicated that the IL6ST gene, an interesting marker of neuroinflammation in FRDA, is a common target gene of both miRNAs. our findings support the evaluation of combined expression levels of different circulating miRNAs as potent epi-biomarkers in FRDA. moreover, we found hsa-miR-148a-3p significantly over-expressed in Intermediate and late-onset friedreich ataxia patients' group (IOG and LOG, respectively) compared to healthy individuals, indicating it as a putative prognostic biomarker in this pathology.
22-mag-2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03
Settore MED/46
English
Con Impact Factor ISI
Biomarkers
Frataxin
Friedreich ataxia
RNA-seq
microRNA
A part of this study was supported by the Italian Ministry of Health - GENERA (Genoma mEdiciNa pERsonalizzatA) - CUP E83C22004130005 – to G.N. Author information
https://humgenomics.biomedcentral.com/articles/10.1186/s40246-024-00602-y#Fun
Vancheri, C., Quatrana, A., Morini, E., Mariotti, C., Mongelli, A., Fichera, M., et al. (2024). An RNA-seq study in Friedreich ataxia patients identified hsa-miR-148a-3p as a putative prognostic biomarker of the disease. HUMAN GENOMICS, 18(1) [10.1186/s40246-024-00602-y].
Vancheri, C; Quatrana, A; Morini, E; Mariotti, C; Mongelli, A; Fichera, M; Rufini, A; Condò, I; Testi, R; Novelli, G; Malisan, F; Amati, F...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/365023
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