microRNA-mRNA expression profiles in the skeletal muscle of myotonic dystrophy type 1

ABSTRACT

Objectives

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism.

Methods

We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1.

Results

Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2.

Conclusion

Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.

KEYWORDS:

• Bioinformatics
• microarray analysis
• microRNA
• myotonic dystrophy
• luciferase reporter assay

Acknowledgments

We extend our sincere gratitude to all the patients and the Orthopedics Department of the Chinese PLA General Hospital for their assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

ML and ZW: literature search. XH and ZW: experiment design. YL and FC: Clinical data acquisition. FY and HW: genetic analysis. QS: muscle biopsy and histopathological analysis. ML: experimental studies. ML and YL: data analysis, statistical analysis and manuscript preparation. XH: critical revision and final approval of the manuscript. All authors contributed to the review of this manuscript and approved the submitted version.

Ethics approval and consent to participate

The study received approval from the Ethics Committee of the Chinese PLA General Hospital (No. S2022-737-01). I confirm that all methods were performed in accordance with the relevant guidelines. All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All human specimens were obtained after receiving written informed consent.

Consent for publication

Written consent was given in writing by all subjects.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2024.2339102

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.