Abstract
Friedreich's ataxia (FRDA) is a multisystem disease affecting the predominately nervous
system, followed by muscle, heart, and pancreas. Current research focused on therapeutic
interventions aimed at molecular amelioration, but there are no reliable noninvasive
signatures available to understand disease pathogenesis. The present study investigates
the alterations of plasma cell-free microRNAs (miRNAs) in FRDA patients and attempts
to find the significance in relevance with the pathogenesis. Total RNA from the plasma
of patients and healthy controls were subjected to miRNA microarray analysis using
Agilent Technologies microarray platform. Differentially regulated miRNAs were validated
by SYBR-green real-time polymerase chain reaction (Thermo Fisher Scientific). The
study identified 20 deregulated miRNAs (false discovery rate < 0.01, fold change ≥ 2.0
≤) in comparison with healthy controls; out of which 17 miRNAs were upregulated, and
3 miRNAs were downregulated. Target and pathway analysis of these miRNAs have shown
association with neurodegenerative and other clinical features in FRDA. Further validation
(n = 21) identified a set of significant (p < 0.05) deregulated miRNAs; hsa-miR-15a-5p, hsa-miR-26a-5p, hsa-miR-29a-3p, hsa-miR-223–3p,
hsa-24–3p, and hsa-miR-21–5p in comparison with healthy controls. These miRNAs were
reported to influence various pathological features associated with FRDA. The present
study is expected to aid in the understanding of disease pathogenesis.
Keywords
Friedreich's ataxia - biomarker - ataxia - microRNA - miRNA
