Micro-RNA expression in muscle and fiber morphometry in myotonic dystrophy type 1

Abstract

We aimed to explore the cellular action of micro-RNAs that are non-coding-RNAs modulating gene expression, whose expression is dysregulated in myotonic dystrophy (DM1). Basic procedure was to measure the levels of muscle-specific myo-miRNAs (miR-1, miR-133a/b, miR-206) in muscle of 12 DM1 patients. Muscle fiber morphometry and a new grading of histopathological severity score were used to compare specific myo-miRNA level and fiber atrophy. We found that the levels of miR-1 and miR-133a/b were significantly decreased, while miR-206 was significantly increased as compared to controls. The histopathological score did not significantly correlate with the levels of myo-miRNAs, even if the lowest levels of miRNA-1 and miRNA-133a/b, and the highest levels of miRNA-206 were observed in patients with either severe histopathological scores or long disease duration. The histopathological score was inversely correlated with disease duration. Nowadays that DM1 muscle biopsies are scanty, since patients are usually diagnosed by genetic analysis, our study offers a unique opportunity to present miRNA expression profiles in muscle and correlate them to muscle morphology in this rare multisystem disorder. Our molecular and morphologic data suggest a post-transcriptional regulatory action of myo-miRNA in DM1, highlighting their potential role as biomarkers of muscle plasticity.

High-throughput analysis of the RNA-induced silencing complex in myotonic dystrophy type 1 patients identifies the dysregulation of miR-29c and its target ASB2

“…Different studies highlighted miRNA dysregulation in DM1 12 – 16 . However, the functional consequences of this dysregulation are far from being elucidated.…”

“…Adding complexity to the molecular pathology of DM1, several other disease mechanisms have been recently found, including microRNA (miRNA) dysregulation 12 – 16 . miRNAs are short non-coding RNAs, which regulate gene expression by decreasing their target mRNA levels, or by blocking their translation 17 – 19 .…”

“…miRNA/target interaction is mediated by the RNA-Induced Silencing Complex (RISC), of which AGO2 is an obligatory component. The levels of a subset of miRNAs, both muscle specific (miR-206, miR-1) and not (miR-335, miR-29b, miR-29c, and miR-33), have been found to be deregulated in DM1 12 – 16 . For miR-1 and miR-206, contrasting data have been reported, probably depending on the low numerosity of DM1 patients studied and the disease severity, as well as the type of skeletal muscle analyzed.…”

An Overview of Alternative Splicing Defects Implicated in Myotonic Dystrophy Type I

“…Many microRNAs are expressed in a tissue-specific manner and show different expression patterns in development and disease [ 121 ]. In DM1, a group of microRNAs known as myomiRs (miR-1, miR-133a/b and miR-206) as well as other microRNAs, have been extensively studied in order to create a DM1 microRNA deregulation profile to help understand DM1 pathological features or to be used as disease biomarkers or therapeutic targets [ 122 , 123 ]. Indeed, specific microRNAs are detected in peripheral blood plasma of DM1 patients which inversely correlate with skeletal muscle strength, and they have been proposed as non-invasive biomarkers of the disease, even though further studies are needed [ 124 ].…”

Of Mice and Men: Advances in the Understanding of Neuromuscular Aspects of Myotonic Dystrophy

“…miRNA profiling revealed significant changes in the heart ( 113 ), skeletal muscle ( 114 – 118 ) and serum ( 119 ) of DM1 and/or DM2 patients. Despite the divergence of some of the results reported, miRNA dysregulation emerged as a disease feature, which could either be a direct consequence of RNA toxicity, or a lateral event secondary to altered cell physiology.…”