Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, 20097 Milan, Italy.
Neuromuscul Disord. 2011 Feb;21(2):81-8. doi: 10.1016/j.nmd.2010.11.012. Epub 2010 Dec 18.
Myotonic Dystrophy Type-1 (DM1) is caused by the expansion of a CTG repeat with a peculiar pattern of multisystemic involvement affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system. Since microRNA expression is disrupted in several myopathies, the expression of 24 candidate microRNAs was analyzed in skeletal muscle biopsies of 15 DM1 patients. Controls were constituted by biopsies without overt pathological features derived from 14 subjects with suspected neuromuscular disorder of undetermined nature. We found that miR-1 and miR-335 were up-regulated, whereas miR-29b and c, and miR-33 were down-regulated in DM1 biopsies compared to controls. We also found that the cellular distribution of muscle specific miR-1, miR-133b and miR-206 was severely altered in DM1 skeletal muscles. MicroRNA dysregulation was likely functionally relevant, since it impacted on the expression of the predicted miR-1, and miR-29 targets. The observed miRNA dysregulations and myslocalizations may contribute to DM1 pathogenetic mechanisms.
强直性肌营养不良症 1 型（DM1）是由 CTG 重复扩展引起的，具有多系统受累的特殊模式，影响骨骼肌、心脏、眼睛、中枢神经系统和内分泌系统。由于几种肌病的 microRNA 表达被打乱，我们分析了 15 名 DM1 患者的骨骼肌活检中的 24 种候选 microRNA 的表达。对照组由来自 14 名疑似性质不明的神经肌肉障碍患者的无明显病理特征的活检组成。我们发现，与对照组相比，DM1 活检中 miR-1 和 miR-335 上调，而 miR-29b 和 c 以及 miR-33 下调。我们还发现，肌肉特异性 miR-1、miR-133b 和 miR-206 的肌肉细胞分布在 DM1 骨骼肌中严重改变。microRNA 失调可能具有功能相关性，因为它影响了预测的 miR-1 和 miR-29 靶标的表达。观察到的 microRNA 失调和肌内定位可能有助于 DM1 的发病机制。
