Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy.

Abstract

Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the first study reporting miRNA as potential biomarkers for oculopharyngeal muscular dystrophy (OPMD), an adult-onset myopathy. We hypothesized that miRNA that is differentially expressed in affected muscles from OPMD patients is secreted to biofluids and those miRNAs could be used as biomarkers for OPMD. We first identified candidate miRNAs from OPMD-affected muscles and from muscles from an OPMD mouse model using RNA sequencing. We then compared the OPMD-deregulated miRNAs to the literature and, subsequently, we selected a few candidates for expression studies in serum and saliva biofluids using qRT-PCR. We identified 126 miRNAs OPMD-deregulated in human muscles, but 36 deregulated miRNAs in mice only (pFDR < 0.05). Only 15 OPMD-deregulated miRNAs overlapped between the in humans and mouse studies. The majority of the OPMD-deregulated miRNAs showed opposite deregulation direction compared with known muscular dystrophies miRNAs (myoMirs), which are associated. In contrast, similar dysregulation direction was found for 13 miRNAs that are common between OPMD and aging muscles. A significant age-association (p < 0.05) was found for 17 OPMD-deregulated miRNAs (13.4%), whereas in controls, only six miRNAs (1.4%) showed a significant age-association, suggesting that miRNA expression in OPMD is highly age-associated. miRNA expression in biofluids revealed that OPMD-associated deregulation in saliva was similar to that in muscles, but not in serum. The same as in muscle, miRNA expression levels in saliva were also found to be associated with age (p < 0.05). Moreover, the majority of OPMD-miRNAs were found to be associated with dysphagia as an initial symptom. We suggest that levels of specific miRNAs in saliva can mark muscle degeneration in general and dysphagia in OPMD.

• Authors: Vered Raz, Rosemarie H M J M Kroon, Hailiang Mei, Muhammad Riaz, Henk Buermans, Saskia Lassche, Corinne Horlings, Bert De Swart, Johanna Kalf, Pradeep Harish, John Vissing, Szymon Kielbasa, Baziel G M van Engelen
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 17 (Aug 22 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32842713 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• MicroRNAs

Topics

• Adult
• Age Factors
• Aged
• Animals
• Biomarkers
• Case-Control Studies
• Deglutition Disorders (genetics)
• Disease Models, Animal
• Gene Expression
• Humans
• MicroRNAs (analysis, blood, genetics)
• Muscle, Skeletal (physiopathology)
• Muscular Dystrophy, Oculopharyngeal (etiology, genetics)
• Saliva (physiology)
• Sequence Analysis, RNA