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

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

Incomplete Penetrance in LGMD1F.

LGMD1F; cascade genetic screening; incomplete penetrance; limb girdle muscular dystrophy; penetrance rat

The Notch ligand Jagged1 regulates thyroid development in zebrafish; implications for human thyroid disgenesis.

The Notch ligand Jagged1 regulates thyroid development in zebrafish; implications for human thyroid disgenesis

Periostin and epithelial-mesenchymal transition score as novel prognostic markers for leiomyosarcoma, myxo\ufb01brosarcoma, and undifferentiated pleomorphic sarcoma

Purpose: Interpatient clinical variability in soft-tissue sarcomas (STS) highlights the need for novel prognostic markers supporting patient risk strati\ufb01cation. As sarcomas might exhibit a more mesenchymal or a more epithelial state, we focused on epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/ MET) for prognostic clues, and selected three histotypes with variable aggressiveness. Experimental Design: The expression of EMT/MET-related factors was measured by qRT-PCR in 55 tumor samples from patients with leiomyosarcoma, myxo\ufb01brosarcoma, or undifferentiated pleomorphic sarcoma. The identi\ufb01ed marker was further evaluated by IHC in 31 leiomyosarcomas and by measuring its circulating levels in 67 patients. The prognostic value of a sarcoma-tailored EMT score was analyzed. Epirubicin chemosensitivity and migration were studied in primary STS cultures. Associations with overall survival (OS) were assessed using Kaplan-Meier and Cox regression methods. Results: High expression of periostin, a mesenchymal matricellular protein, in sarcoma tissues (P \ubc 0.0024), its high stromal accumulation in leiomyosarcomas (P \ubc 0.0075), and increased circulation (>20 ng/mL, P \ubc 0.0008) were associated with reduced OS. High periostin expression [HR 2.9; 95% con\ufb01dence interval (CI), 1.3-6.9; P \ubc 0.0134] and circulation (HR 2.6; 95% CI, 1.3-5.1; P \ubc 0.0086), and a mesenchymal EMT score (mesenchymal vs. transitioning; HR, 5.2; 95% CI, 2.1-13.0, P \ubc 0.0005) were associated with increased risk in multivariable models. An intrinsic or induced mesenchymal state enhanced chemoresistance and migration in sarcoma cell lines. Conclusions: Although limited to a pilot study, these \ufb01ndings suggest that periostin might contribute prognostic information in the three studied STS histotypes. Moreover, a transitioning EMT score measured in the tumor might predict a less active and a more chemosensitive disease