1. Inicio
  2. Publicaciones
  3. Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies

Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • García-Giménez J.L.
  • García-Trevijano E.R.
  • Avilés-Alía A.I.
  • Ibañez-Cabellos J.S.
  • Pallardó F.V.
  • Viña J.R.
  • Zaragozá R.

Abstract

Background: Limb-girdle muscular dystrophy (LGMD) is a rare neuromuscular disease including a growing and heterogeneous number of subtypes with variable phenotype. Their clinical and histopathological characteristics frequently overlap with other neuromuscular dystrophies. Our goal was to identify, by a non-invasive method, a molecular signature including biochemical and epigenetic parameters with potential value for patient prognosis and stratification. Results: Circulating miRNome was obtained by smallRNA-seq in plasma from LGMD patients (n = 6) and matched-controls (n = 6). Data, validated by qPCR in LGMD samples, were also examined in other common muscular dystrophies: Duchenne (DMD) (n = 5) and facioscapulohumeral muscular dystrophy (FSHD) (n = 4). Additionally, biochemical and clinical parameters were analyzed. miRNome analysis showed that thirteen differentially expressed miRs could separate LGMD vs control group by hierarchical clustering. Most of differentially expressed miRs in LGMD patients were up-regulated (miR-122-5p, miR-122b-3p, miR-6511a-3p, miR-192-5p, miR-574-3p, mir-885-3p, miR-29a-3p, miR-4646-3p, miR-203a-3p and miR-203b-5p) whilst only three of sequenced miRs were significantly down-regulated (miR-19b-3p, miR-7706, miR-323b-3p) when compared to matched controls. Bioinformatic analysis of target genes revealed cell cycle, muscle tissue development, regeneration and senescence as the most affected pathways. Four of these circulating miRs (miR-122-5p, miR-192-5p, miR-19b-3p and miR-323b-3p), together with the myomiR miR-206, were further analysed by qPCR in LGMD, DMD and FSHD. The receiver operating characteristic curves (ROC) revealed high area under the curve (AUC) values for selected miRs in all groups, indicating that these miRs have good sensitivity and specificity to distinguish LGMD, DMD and FSHD patients from healthy controls. miR-122-5p, miR-192-5p and miR-323-3p were differentially expressed compared to matched-controls in all groups but apparently, each type of muscular dystrophy showed a specific pattern of miR expression. Finally, a strong correlation between miRs and biochemical data was only found in LGMD patients: while miR-192-5p and miR-122-5p negatively correlated with CK, miR-192-5p positively correlated with vitamin D3 and ALP. Conclusions: Although limited by the small number of patients included in this study, we propose here a specific combination of circulating miR-122-5p/miR-192-5p/miR-323-3 and biochemical parameters as a potential molecular signature whose clinical value for LGMD patient prognosis and stratification should be further confirmed in a larger cohort of patients. © 2022, The Author(s).

Datos de la publicación

ISSN/ISSNe:
1750-1172, 1750-1172

Orphanet Journal of Rare Diseases  BMC

Tipo:
Article
Páginas:
-
PubMed:
36575500
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
1,105 SCImago ℠
Cuartil:
Q1 SCImago ℠

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • Humans; MicroRNAs; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Facioscapulohumeral; circulating microRNA; microRNA 122; microrna 6511a 3p; microrna192 5p; microrna203a 3p; microrna203b 5p; microrna29a 3p; microrna4646 3p; microrna574 3p; microrna885 3p; unclassified drug; microRNA; MIRN206 microRNA, human; adult; Article; breast cancer; cardiomyopathy; clinical article; cohort analysis; controlled study; diagnostic test accuracy study; differential gene expression; Duchenne muscular dystrophy; facioscapulohumeral muscular dystrophy; female; human; limb girdle muscular dystrophy; limb weakness; male; middle aged; real time reverse transcription polymerase chain reaction; receiver operating characteristic; RNA sequencing; sensitivity and specificity; genetics

Cita

Compartir