miR-411 is up-regulated in FSHD myoblasts and suppresses myogenic factors

Episode von Medizin - Open Access LMU - Teil 21/22 von Ludwig-Maximilians-Universität München · 1. Januar 2013

Background: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disorder, which is linked to the contraction of the D4Z4 array at chromosome 4q35. Recent studies suggest that this shortening of the D4Z4 array leads to aberrant expression of double homeobox protein 4 (DUX4) and causes FSHD. In addition, misregulation of microRNAs (miRNAs) has been reported in muscular dystrophies including FSHD. In this study, we identified a miRNA that is differentially expressed in FSHD myoblasts and investigated its function. Methods: To identify misregulated miRNAs and their potential targets in FSHD myoblasts, we performed expression profiling of both miRNA and mRNA using TaqMan Human MicroRNA Arrays and Affymetrix Human Genome U133A plus 2.0 microarrays, respectively. In addition, we over-expressed miR-411 in C2C12 cells to determine the effect of miR-411 on myogenic markers. Results: Using miRNA and mRNA expression profiling, we identified 8 miRNAs and 1,502 transcripts that were differentially expressed in FSHD myoblasts during cell proliferation. One of the 8 differentially expressed miRNAs, miR-411, was validated by quantitative RT-PCR in both primary (2.1 fold, p<0.01) and immortalized (2.7 fold, p<0.01) myoblasts. In situ hybridization showed cytoplasmic localization of miR-411 in FSHD myoblasts. By analyzing both miRNA and mRNA data using Partek Genomics Suite, we identified 4 mRNAs potentially regulated by miR-411 including YY1 associated factor 2 (YAF2). The down-regulation of YAF2 in immortalized myoblasts was validated by immunoblotting (-3.7 fold, p<0.01). C2C12 cells were transfected with miR-411 to determine whether miR-411 affects YAF2 expression in myoblasts. The results showed that over-expression of miR-411 reduced YAF2 mRNA expression. In addition, expression of myogenic markers including Myod, myogenin, and myosin heavy chain 1 (Myh1) were suppressed by miR-411. Conclusions: The study demonstrated that miR-411 was differentially expressed in FSHD myoblasts and may play a role in regulating myogenesis.

Weitere Episoden von „Medizin - Open Access LMU - Teil 21/22“

• A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial 1. Januar 2013
• A new web-based method for automated analysis of muscle histology 1. Januar 2013
• Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study 1. Januar 2013
• Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial 1. Januar 2013
• Aequilibrium prudentis: on the necessity for ethics and policy studies in the scientific and technological education of medical professionals 1. Januar 2013
• An AUC-based permutation variable importance measure for random forests 1. Januar 2013
• Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum 1. Januar 2013
• `Burden to others' as a public concern in advanced cancer: a comparative survey in seven European countries 1. Januar 2013
• Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities 1. Januar 2013
• Conscious Presence and Self Control as a measure of situational awareness in soldiers - A validation study 1. Januar 2013
• Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events 1. Januar 2013
• Current experience with applying the GRADE approach to public health interventions: an empirical study 1. Januar 2013
• Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH 1. Januar 2013
• Diversity of the var gene family of Indonesian Plasmodium falciparum isolates 1. Januar 2013
• A comparative analysis of the properties of regulated promoter systems commonly used for recombinant gene expression in Escherichia coli 1. Januar 2013

Alle Episoden von Medizin - Open Access LMU - Teil 21/22 · Mehr Bildung-Podcasts