Dataset Information

MiRNA expression in control and FSHD fetal human muscle biopsies.

ABSTRACT: BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. METHODS:Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. RESULTS:During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. CONCLUSIONS:This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.

SUBMITTER: Portilho DM

PROVIDER: S-EPMC4333765 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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miRNA expression in control and FSHD fetal human muscle biopsies.

Portilho Débora Morueco DM Alves Marcelo Ribeiro MR Kratassiouk Gueorgui G Roche Stéphane S Magdinier Frédérique F de Santana Eliane Corrêa EC Polesskaya Anna A Harel-Bellan Annick A Mouly Vincent V Savino Wilson W Butler-Browne Gillian G Dumonceaux Julie J

PloS one 20150218 2

<h4>Background</h4>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle developme ...[more]

PMID: 25692472

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Project description:Emerging evidence has demonstrated that miRNA sequences can regulate skeletal myogenesis by controlling the process of myoblast proliferation and differentiation. However, at present a deep analysis of miRNA expression in control and FSHD myoblasts during differentiation has not yet been derived. To close this gap, we used a next-generation sequencing (NGS) approach applied to in vitro myogenesis. Furthermore, to minimize sample genetic heterogeneity and muscle-type specific patterns of gene expression, miRNA profiling from NGS data was filtered with FC ≥ 4 (log(2)FC ≥ 2) and p-value<0.05, and its validation was derived by qRT-PCR on myoblasts from seven muscle districts. In particular, control myogenesis showed the modulation of 38 miRNAs, the majority of which (34 out 38) were up-regulated, including myomiRs (miR-1, -133a, -133b and -206). Approximately one third of the modulated miRNAs were not previously reported to be involved in muscle differentiation, and interestingly some of these (i.e. miR-874, -1290, -95 and -146a) were previously shown to regulate cell proliferation and differentiation. FSHD myogenesis evidenced a reduced number of modulated miRNAs than healthy muscle cells. The two processes shared nine miRNAs, including myomiRs, although with FC values lower in FSHD than in control cells. In addition, FSHD cells showed the modulation of six miRNAs (miR-1268, -1268b, -1908, 4258, -4508- and -4516) not evidenced in control cells and that therefore could be considered FSHD-specific, likewise three novel miRNAs that seem to be specifically expressed in FSHD myotubes. These data further clarify the impact of miRNA regulation during control myogenesis and strongly suggest that a complex dysregulation of miRNA expression characterizes FSHD, impairing two important features of myogenesis: cell cycle and muscle development. The derived miRNA profiling could represent a novel molecular signature for FSHD that includes diagnostic biomarkers and possibly therapeutic targets.

Project description:The sheep is an economically important animal, and there is currently a major focus on improving its meat quality through breeding. There are variations in the growth regulation mechanisms of different sheep breeds, making fundamental research on skeletal muscle growth essential in understanding the regulation of (thus far) unknown genes. Skeletal muscle development is a complex biological process regulated by numerous genes and non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). In this study, we used deep sequencing data from sheep longissimus dorsi (LD) muscles sampled at day 60, 90, and 120 of gestation, as well as at day 0 and 360 following birth, to identify and examine the lncRNA and miRNA temporal expression profiles that regulate sheep skeletal myogenesis. We stained LD muscles using histological sections to analyse the area and circumference of muscle fibers from the embryonic to postnatal development stages. Our results showed that embryonic skeletal muscle growth can be characterized by time. We obtained a total of 694 different lncRNAs and compared the differential expression between the E60 vs. E90, E90 vs. E120, E120 vs. D0, and D0 vs. D360 lncRNA and gene samples. Of the total 701 known sheep miRNAs we detected, the following showed a wide range of expression during the embryonic stage: miR-2387, miR-105, miR-767, miR-432, and miR-433. We propose that the detected lncRNA expression was time-specific during the gestational and postnatal stages. GO and KEGG analyses of the genes targeted by different miRNAs and lncRNAs revealed that these significantly enriched processes and pathways were consistent with skeletal muscle development over time across all sampled stages. We found four visual lncRNA-gene regulatory networks that can be used to explore the function of lncRNAs in sheep and may be valuable in helping improve muscle growth. This study also describes the function of several lncRNAs that interact with miRNAs to regulate myogenic differentiation.

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MiRNA expression in control and FSHD fetal human muscle biopsies.

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miRNA expression in control and FSHD fetal human muscle biopsies.

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