Identification of serum microRNAs as potential biomarkers in Pompe disease

Abstract

Objective To analyze the microRNA profile in serum of patients with Adult Onset Pompe disease (AOPD). Methods We analyzed the expression of 185 microRNAs in serum of 15 AOPD patients and five controls using microRNA PCR Panels. The expression levels of microRNAs that were deregulated were further studied in 35 AOPD patients and 10 controls using Real‐Time PCR. Additionally, the skeletal muscle expression of microRNAs which showed significant increase levels in serum samples was also studied. Correlations between microRNA serum levels and muscle function test, spirometry, and quantitative muscle MRI were performed (these data correspond to the study NCT01914536 at ClinicalTrials.gov). Results We identified 14 microRNAs that showed different expression levels in serum samples of AOPD patients compared to controls. We validated these results in a larger cohort of patients and we found increased levels of three microRNAs, the so called dystromirs: miR‐1‐3p, miR‐133a‐3p, and miR‐206. These microRNAs are involved in muscle regeneration and the expression of these was increased in patients' muscle biopsies. Significant correlations between microRNA levels and muscle function test were found. Interpretation Serum expression levels of dystromirs may represent additional biomarkers for the follow‐up of AOPD patients.

Downregulation of miR-335-5P in Amyotrophic Lateral Sclerosis Can Contribute to Neuronal Mitochondrial Dysfunction and Apoptosis

“…The tubes were then centrifuged at 1800 rpm for 10 minutes. miRNA extraction was performed as previously described 45 .miRNAs were isolated from serum using the miRCURY RNA Isolation Kit -Biofluids www.nature.com/scientificreports www.nature.com/scientificreports/ (Qiagen). 200 µl of serum were lysed with lysis solution following manufacturer's instructions.…”

“…Normality and homogeneity of variance tests were performed. The data conforming to normal distribution and homogeneity of variance were expressed as mean ± standard deviation and analyzed with t-test 45 . P values of <0.05 are indicated with one asterisk (*) and P values of less or equal than 0.01 are indicated with two asterisks (**).…”

Pompe Disease: New Developments in an Old Lysosomal Storage Disorder

“…The search for reliable biomarkers to aid in diagnosis, progression, and response to ERT has remained elusive over the past decades. In this regard, of particular interest is the recent identification of circulating microRNAs as potential biomarkers of Pompe disease [ 52 , 53 ] (reviewed in [ 54 ]). These new biomarkers, in particular miR-133a, can help monitor the efficacy of the current and emerging therapies by serial sampling through liquid biopsies.…”

Highlights on Genomics Applications for Lysosomal Storage Diseases

“…For the past few years, the search for new biomarkers has shifted towards microRNAs [ 86 , 87 , 88 ], opening an interesting perspective for genomics applications. Indeed, specific patterns of circulating miRNAs can identify patients with Fabry or Pompe diseases, and they could be useful for predicting the evolution of the disease or for assessing responses to therapy as well.…”

“…Indeed, specific patterns of circulating miRNAs can identify patients with Fabry or Pompe diseases, and they could be useful for predicting the evolution of the disease or for assessing responses to therapy as well. Some of these miRNAs, in particular, were associated with heart problems and endothelial dysfunctions in Fabry patients, or they significantly correlated with phenotype severity, muscle dysfunctions, and Pompe disease-related patho/pathways (autophagy, muscle regeneration, muscle atrophy) [ 86 , 87 , 88 ].…”