Plasma microRNA miR-26b as a potential diagnostic biomarker of degenerative myelopathy in Pembroke welsh corgis

Abstract

Background Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Most DM-affected PWCs are homozygous for the mutant superoxide dismutase 1 ( SOD1 ) allele; however, the genetic examination for the SOD1 mutation does not exclusively detect symptomatic dogs. In order to identify novel biomarkers, the plasma microRNA (miRNA) profiles of PWCs with DM were investigated. Results Quantification of the plasma levels of 277 miRNAs by an RT-qPCR array identified 11 up-regulated miRNAs and 7 down-regulated miRNAs in DM-affected PWCs from those in wild-type SOD1 PWCs. A pathway analysis identified 3 miRNAs: miR-26b, miR-181a, and miR-196a, which potentially regulate several genes associated with SOD1. In order to validate the diagnostic accuracy of the candidate miRNAs in the aged PWC population, candidate miRNAs in plasma were measured by RT-qPCR and a receiver operating characteristic (ROC) curve analysis was performed. miR-26b had the largest area under the ROC curve for distinguishing DM PWCs from healthy PWCs (sensitivity, 66.7%; specificity, 87.0%). The plasma level of miR-26b was significantly higher in the DM group than in the healthy control group. A positive correlation was observed between increases in the plasma level of miR-26b and disease progression. Conclusions These results suggest that plasma miR-26b is a potential novel diagnostic biomarker of DM. Electronic supplementary material The online version of this article (10.1186/s12917-019-1944-3) contains supplementary material, which is available to authorized users.

Downregulation of miR-26b-5p, miR-204-5p, and miR-497-3p Expression Facilitates Exercise-Induced Physiological Cardiac Hypertrophy by Augmenting Autophagy in Rats

“…The 10-week moderate-intensity swimming exercise enlarged and thickened cardiomyocytes. Although an increase in cardiomyocyte volume is also observed in pathological cardiomegaly, increased fetal gene expression such as ANP, BNP, b-MHC were also significantly upregulated in pathological LVH (Swynghedauw, 1986;Dorn et al, 1994;Bernardo et al, 2010;Nakamura and Sadoshima, 2018;Oldfield et al, 2019). In our swimming exercise-induced cardiomyocyte hypertrophy, the expression of ANP, a-actin, and the ratio of b-MHC to a-MHC was not significantly changed, indicating a physiological LVH model was successfully induced.…”

“…Given LVH in response to endurance exercise is protective, the miRNA changes in physiological LVH is supposed to be adaptive and to promote moderate autophagy which is essential for physiological LVH. Of note, miR-26b-5p, miR-204-5p, and miR-497-3p had been detected in plasma and were used as a potential diagnostic biomarker for diseases such as lung cancer (Du et al, 2015;Guo et al, 2015;Lu et al, 2018;Nakata et al, 2019). Distinct plasma gradients of miR-204-5p in the pulmonary circulation were observed in patients with different pulmonary hypertension subtypes (Estephan et al, 2019).…”

“…Both of them have an increased myocyte volume and heart size. The difference is that physiological LVH is induced by aerobic exercise training, postnatal growth, and pregnancy, and characterized by unchanged fetal and apoptosis gene expression and increased cardiac function while pathological LVH is stimulated by pressure or volume overload or cardiomyopathy, and characterized by apoptosis and fibrosis and depressed cardiac function (Bernardo et al, 2010;Nakamura and Sadoshima, 2018;Oldfield et al, 2019). For example, LVH induced by swimming exercise training is an adaption for a chronic increase in hemodynamic overload (Xiao et al, 2014;Bernardo et al, 2018), whereas myocardial infarction induced pathological LVH is associated with increased fibrosis, lowered aerobic capacity, and maladaptive remodeling (McMullen and Izumo, 2006;Dorn, 2007;Schiattarella and Hill, 2015).…”

MiR-26b Suppresses the Development of Stanford Type A Aortic Dissection by Regulating HMGA2 and TGF-β/Smad3 Signaling Pathway

“…Previous studies have showed that miR-26b served as a novel diagnostic biomarker for degenerative myelopathy. 22) Moreover, by regulating DEPDC1 gene, miR-26b acted as a tumor suppressor in triple negative breast cancer. 23) Ovchinnikova et al found that miR-26b was associated with increasing acuity of heart failure.…”

Genetic insights in canine degenerative myelopathy

“…Aside from these routinely used diagnostic techniques, new molecular techniques are being developed. In a recent study on PWCs, a positive correlation between increases in the plasma levels of miR-26b and disease progression has been discovered (Nakata et al, 2019). MiR-26b is a microRNA (miRNA), i.e.…”