| First Author | Cerro-Herreros E | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 2482 |
| PubMed ID | 29946070 | Mgi Jnum | J:267877 |
| Mgi Id | MGI:6209348 | Doi | 10.1038/s41467-018-04892-4 |
| Citation | Cerro-Herreros E, et al. (2018) miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models. Nat Commun 9(1):2482 |
| abstractText | Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). We previously showed the efficacy of miRNA downregulation in Drosophila DM1 model. Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. Antagonists of miR-23b and miR-218 miRNAs enhance MBNL protein levels and rescue pathogenic missplicing events in DM1 myoblasts. Systemic delivery of these "antagomiRs" similarly boost MBNL expression and improve DM1-like phenotypes, including splicing alterations, histopathology, and myotonia in the HSA(LR) DM1 model mice. These mammalian data provide evidence for therapeutic blocking of the miRNAs that control Muscleblind-like protein expression in myotonic dystrophy. |
