Downregulation of miRNA-29, -23 and -21 in Urine of Duchenne Muscular Dystrophy Patients

Abstract

Aim: To study the signature of 87 urinary miRNAs in Duchenne muscular dystrophy (DMD) patients, select the most dysregulated and determine statistically significant differences in their expression between controls, ambulant (A) and nonambulant (NA) DMD patients, and patients on different corticosteroid regimens. Patients/materials & methods: Urine was collected from control (n = 20), A (n = 31) and NA (n = 23) DMD patients. miRNA expression was measured by reverse transcription-quantitative PCR. Results: miR-29c-3p was significantly downregulated in A DMD patients while miR-23b-3p and miR-21-5p were significantly downregulated in NA DMD patients compared with age-matched controls. Conclusion: miR-29c-3p, miR-23b-3p and miR-21-5p are promising novel noninvasive biomarkers for DMD, and miR-29c-3p levels are differentially affected by different steroid regimens, supporting the antifibrotic effect of steroid therapy.

Keywords::

• biomarker
• deflazacort
• Duchenne muscular dystrophy
• exosome
• miRNA
• prednisolone

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2018-0022.

Disclosure

All research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This research was performed at the Dubowitz Neuromuscular Centre (London, UK) with the collaboration of the Institute of Myology (Paris, France), the Muscular Dystrophy Research Centre (Newcastle, UK), the Leiden University Medical Center (Leiden, The Netherlands) and the UMC St Radboud (Nijmegen, The Netherlands).

Financial & competing interests disclosure

This work was supported by the Association Francaise Contre Les Myopathies. V Ricotti is currently an employee of Solid Biosciences. F Muntoni has received consulting fees from Biogen, Italfarmaco, Pfizer, PTC Therapeutics, Roche, Sarepta Therapeutics and Wave Therapeutics; and is supported by the NIH Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The support of the MRC Neuromuscular Centre Biobank and of the Muscular Dystrophy UK is also gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the Association Francaise Contre Les Myopathies. V Ricotti is currently an employee of Solid Biosciences. F Muntoni has received consulting fees from Biogen, Italfarmaco, Pfizer, PTC Therapeutics, Roche, Sarepta Therapeutics and Wave Therapeutics; and is supported by the NIH Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The support of the MRC Neuromuscular Centre Biobank and of the Muscular Dystrophy UK is also gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.