The role of microRNAs in skeletal muscle health and disease

Kirby, Tyler J.; Chaillou, Thomas; McCarthy, John J.

doi:10.2741/4298

Cited by 56 publications

(22 citation statements)

References 218 publications

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“…Our data contributes to the mounting evidence implicating miRNAs as regulators of exercise-induced adaptations (Zacharewicz et al, 2013; Denham et al, 2014; Kirby et al, 2015). Given miRNAs are responsible for tissue specific gene regulation, it is difficult to compare our data to others because of the novelty of this study examining the impact of long-term endurance exercise on the content of muscle-enriched miRNAs in whole blood.…”

Section: Discussionsupporting

confidence: 59%

“…Circulating miRNAs include those secreted from blood cells and organs in the body, which are primarily transported in microvesicles or RNA-binding proteins (high-density lipoproteins or argonaute 2; Chen et al, 2012). The miRNAs chosen a priori in this study are muscle-enriched miRNAs previously described to regulate important genes in pathways central for skeletal and heart muscle (Wang et al, 2010; Fernandes et al, 2015; Kirby et al, 2015), which made them attractive candidates as exercise biomarkers. For instance, while miR-1 augments myogenesis by deregulating its target mRNA, histone deacetylase ( HDAC4 ), miR-133 promotes myoblast proliferation through inhibition of serum response factor ( SRF ) (Chen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Physiological left ventricular hypertrophy is an adaptation to extensive aerobic exercise training that improves maximum oxygen uptake (O 2 max ) and a number of miRNAs are implicated in this process (e.g., miR-1, miR-21, and miR-133a; Soci et al, 2011; Ma et al, 2013). Skeletal muscle-enriched miRNAs, called myomiRs, are particularly responsive to aerobic and resistance exercise training (Kirby et al, 2015). For example, 12 weeks of exercise training lead to a decrease in miR-1, miR-133a/b, and miR-206 in conjunction with improvements to O 2 max and insulin sensitivity in healthy young men (Nielsen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Muscle-Enriched MicroRNAs Isolated from Whole Blood Are Regulated by Exercise and Are Potential Biomarkers of Cardiorespiratory Fitness

Denham

Prestes

2016

Front. Genet.

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MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression post-transcriptionally. Evidence indicating miRNAs influence exercise-induced health and performance adaptations is mounting. Circulating miRNAs are responsible for intercellular communication and could serve as biomarkers for disease and exercise-related traits. Such biomarkers would contribute to exercise screening, monitoring, and the development of personalized exercise prescription. Accordingly, we investigated the impact of long-term strenuous aerobic exercise training and a single bout of maximal aerobic exercise on five muscle-enriched miRNAs implicated in exercise adaptations (miR-1, miR-133a, miR-181a, miR-486, and miR-494). We also determined linear correlations between miRNAs, resting heart rate, and maximum oxygen uptake (O2 max). We used TaqMan assay quantitative polymerase chain reaction to analyze the abundance of miR-1, miR-133a, miR-181a, miR-486, and miR-494 in resting whole blood of 67 endurance athletes and 61 healthy controls. Relative to controls, endurance athletes exhibited increased miR-1, miR-486, and miR-494 content (1.26- to 1.58-fold change, all p < 0.05). miR-1, miR-133a, and miR-486 were decreased immediately after maximal aerobic exercise (0.64- to 0.76-fold change, all p < 0.01) performed by 19 healthy, young men (20.7 ± 2.4 years). Finally, we observed positive correlations between miRNA abundance and O2 max (miR-1 and miR-486) and an inverse correlation between miR-486 and resting heart rate. Therefore, muscle-enriched miRNAs isolated from whole blood are regulated by acute and long-term aerobic exercise training and could serve as biomarkers of cardiorespiratory fitness.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Muscle-Enriched MicroRNAs Isolated from Whole Blood Are Regulated by Exercise and Are Potential Biomarkers of Cardiorespiratory Fitness

Denham

Prestes

2016

Front. Genet.

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“…One such epigenetic factor that has shown promise is microRNAs (miRNA)—small noncoding RNAs that modulate gene expression. miRNAs have been identified to play a key role in heart failure and may be a potentially useful prognostic marker in cardiovascular disease, as well as in skeletal myopathies [reviewed in (151,314)].…”

Section: Resultsmentioning

confidence: 99%

Overview of the Muscle Cytoskeleton

Henderson

Gomez

Novak

et al. 2017

Comprehensive Physiology

220

193

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Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments. The costamere, on the other hand, tethers the sarcomere to the cell membrane. Unique structures like the intercalated disc in cardiac muscle and the myotendinous junction in skeletal muscle help synchronize and transmit force. Intense investigation has been done on many of the proteins that make up these cytoskeletal assemblies. Yet the details of their function and how they interconnect have just started to be elucidated. A vast number of human myopathies are contributed to mutations in muscle proteins; thus understanding their basic function provides a mechanistic understanding of muscle disorders. In this review, we highlight the components of striated muscle with respect to their interactions, signaling pathways, functions, and connections to disease.

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“…[13–15] miRs are small, ~22 base pair non-coding RNAs that are recognized for having major roles in biology and disease. [16–18] miRs bind to sequences in the 3’ UTR of target mRNAs and inhibit translation, promote mRNA degradation or both. In most cases, miRs bind with partial complementarity to one or more sequences within a target mRNA.…”

Section: Introductionmentioning

confidence: 99%

The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling

et al. 2016

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Spinal cord injury (SCI) results in muscle atrophy, reduced force generation and an oxidative-to-glycolytic fiber type shift. The mechanisms responsible for these alterations remain incompletely understood. To gain new insights regarding mechanisms involved in deterioration of muscle after SCI, global expression profiles of miRs in paralyzed gastrocnemius muscle were compared between sham-operated (Sham) and spinal cord-transected (SCI) rats. Ingenuity Pathways Analysis of the altered miRs identified signaling via insulin, IGF-1, integrins and TGF-β as being significantly enriched for target genes. By qPCR, miRs 23a, 23b, 27b, 145, and 206, were downregulated in skeletal muscle 56 days after SCI. Using FISH, miR-145, a miR not previously implicated in the function of skeletal muscle, was found to be localized to skeletal muscle fibers. One predicted target of miR-145 was Cited2, a transcriptional regulator that modulates signaling through NF-κB, Smad3 and other transcription factors. The 3’ UTR of Cited2 mRNA contained a highly conserved miR-145 seed sequence. Luciferase reporter assays confirmed that miR-145 interacts with this seed sequence. However, Cited2 protein levels were similar between Sham and SCI groups, indicating a biochemical interaction that was not involved in the context of adaptations after SCI. Taken together, the findings indicate dysregulation of several highly expressed miRs in skeletal muscle after SCI and suggest that reduced expression of miR-23a, 145 and 206 may have roles in alteration in skeletal muscle mass and insulin responsiveness in muscle paralyzed by upper motor neuron injuries.

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The role of microRNAs in skeletal muscle health and disease

Cited by 56 publications

References 218 publications

Muscle-Enriched MicroRNAs Isolated from Whole Blood Are Regulated by Exercise and Are Potential Biomarkers of Cardiorespiratory Fitness

Muscle-Enriched MicroRNAs Isolated from Whole Blood Are Regulated by Exercise and Are Potential Biomarkers of Cardiorespiratory Fitness

Overview of the Muscle Cytoskeleton

The Signature of MicroRNA Dysregulation in Muscle Paralyzed by Spinal Cord Injury Includes Downregulation of MicroRNAs that Target Myostatin Signaling

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