Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1

Abstract

Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.

Identification of serum microRNAs as potential biomarkers in Pompe disease

“…Several reports have demonstrated that miRNAs are potential biomarkers of different diseases, such as cancer, liver injury, or heart failure . The expression profile of miRNAs has also been studied in different muscle diseases such as DMD, myotonic dystrophy, and FSHD . In these studies, several miRNAs have a different pattern of expression when compared to controls.…”

Release of MicroRNAs into Body Fluids from Ten Organs of Mice Exposed to Cigarette Smoke

“…Exposure to MCS caused skeletal muscle atrophy also in a mouse model of COPD 43 and upregulated several pathways of metabolic processes and tissue degradation in muscles 56 . Evaluation of circulating miRNAs in myotonic dystrophy patients suggested that miRNAs might be useful as humoral biomarkers of that muscle disease 57 . The poor correlation between early alterations of miRNA profiles in the lung and in the blood serum of MCS-exposed mice is in agreement with the results of a previous study in mice exposed to the same agent during the first 4 months of life and thereafter kept in filtered air for an additional 3.5 months, when smoking-related lung tumors were detectable 9 .…”

Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder

“…Studies on mouse and rat models have also proved its involvement in spermatogenesis (Luo et al, 2015 ) and testis differentiation (Rakoczy et al, 2013 ), chondrogenesis and growth (Pando et al, 2012 ; Waki et al, 2016 ), and sensitivity of fetal neural development to ethanol and nicotine (Balaraman et al, 2012 ). Circulating miR-140-3p has been identified as dysregulated in either plasma or serum from patients with different pathological conditions and it has already been suggested as a potential biomarker for some of them, like myotonic dystrophy type 1 and type 2 (Perfetti et al, 2014 , 2016 ), biliary atresia (Peng X. et al, 2016 ), papillary thyroid carcinoma (Li et al, 2015 ), wet age-related macular degeneration (Ertekin et al, 2014 ), and myasthenia gravis (Nogales-Gadea et al, 2014 ). Its potential as non-invasive intracellular biomarker has also been demonstrated on blood samples from patients affected by coronary artery disease (Taurino et al, 2010 ; Karakas et al, 2017 ) and type 2 diabetes mellitus, (Collares et al, 2013 ).…”