Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy

Qi Meng; Jiapeng Zhang; Jingzi Zhong; Dan Zeng; Dan Lan

doi:10.3389/fneur.2022.921785

Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy

Front Neurol. 2022 Jul 6:13:921785. doi: 10.3389/fneur.2022.921785. eCollection 2022.

Authors

Qi Meng¹, Jiapeng Zhang¹, Jingzi Zhong¹, Dan Zeng¹, Dan Lan¹

Affiliation

¹ Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Abstract

Creatine kinase (CK) as a biomarker has long been expected to be replaced by other fluid biomarkers for Duchenne muscular dystrophy (DMD) because it is independent of disease severity. Growing evidence has demonstrated that muscle-specific microRNAs, known as myomiRs, can act as biomarkers for monitoring muscle pathology and disease severity of DMD patients. To gain insights into the relationship between serum myomiRs and clinical assessment, we measured serum levels of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 in 48 DMD patients by using real-time quantitative reverse transcription polymerase chain reaction. These were then compared with age, muscle strength, muscle functions, CK levels, cardiac manifestations, and mutation types (deletions, duplications, and small mutations). When compared to 53 controls, the expression levels of myomiRs were all significantly elevated (p < 0.05). The receiver operating characteristic curves of all seven myomiRs reflected marked differences between DMD patients and healthy controls (p < 0.05). We also showed that serum levels of myomiRs were positively correlated with lower limb distal muscle strength in patients of all age groups. The levels of miR-499, miR-208b, miR-133a, and miR-133b had significant negative correlations with the time to be upright from the supine position (Gowers' time) and the time taken to climb four stairs in DMD patients older than 7 years. Serum levels of miR-1, miR-133a, miR-133b, and miR-499 in patients with cardiac involvement were remarkably higher than those in non-cardiac-involved patients. There was no significant difference in levels of myomiRs between the different mutation groups. Our results indicated that serum myomiRs could be considered as novel biomarkers for monitoring pathology/pathophysiology of DMD patients. In particular, miR-499, miR-208b, miR-133a, and miR-133b might have the ability to reflect the extent of muscle impairment.

Keywords: Duchenne muscular dystrophy; biomarker; child; creatine kinase; microRNA; myomiRs.