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Neuropediatrics 2018; 49(01): 035-043
DOI: 10.1055/s-0037-1607279
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Differentially Regulated Cell-Free MicroRNAs in the Plasma of Friedreich's Ataxia Patients and Their Association with Disease Pathology

Subrahamanyam Dantham   *
1   Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
,
Achal K. Srivastava
2   Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
,
Sheffali Gulati
3   Department of Paediatrics Neurology, All India Institute of Medical Sciences, New Delhi, India
,
Moganty R. Rajeswari
1   Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations
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Publication History

01 May 2017

28 August 2017

Publication Date:
27 November 2017 (online)

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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

Funding

The authors received financial support from the Indian Council of Medical Research, New Delhi (ref. no. 5/4–5/85/Neuro/2012-NCD-I) for the research, authorship, and/or publication of this article. We acknowledge Department of Biotechnology, Government of India for providing research fellowship to D.S.


Ethical Approval

The study design was approved by the institute ethics committee (ref. no. IEC/NP-311/2012/RP-24/2012).


* The present address: National Institute of Malaria Research (Indian Council of Medical Research), New Delhi, India.


Supplementary Material

 

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