Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy.
Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy.
复制标题
DOI：
10.1038/mtna.2016.47
复制
发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
鉴定无创生物标志物来监测脊髓性肌萎缩症（SMA）的疾病进展变得越来越重要。MicroRNAs （miRNAs）调节基因表达，并参与神经肌肉疾病的发病机制，包括运动神经元变性。在这项研究中，我们选择性地表征了miR-9、miR-206和miR-132在SMA转基因小鼠的脊髓、骨骼肌和血清以及SMA患者血清中的表达。系统分析了不同疾病严重程度（重度i型和轻度iii型）、不同疾病分期（症状前期、中期和晚期）以及morpholino反义寡核苷酸处理小鼠的miRNA表达情况。这三种mirna在SMA小鼠脊髓、骨骼肌和血清样本中均有差异表达。在症状前阶段，脊髓和骨骼肌发生变化之前，血清mirna发生改变。单剂量morpholino反义寡聚物PMO25治疗SMA小鼠后，脊髓、肌肉和血清中改变的miR-132水平瞬间逆转至正常水平。我们还证实了SMA患者血清样本中miR-9和miR-132水平的显著改变。我们的研究表明，mirna作为SMA的非侵入性生物标志物具有潜力。
The identification of noninvasive biomarkers to monitor the disease progression in spinal muscular atrophy (SMA) is becoming increasingly important. MicroRNAs (miRNAs) regulate gene expression and are implicated in the pathogenesis of neuromuscular diseases, including motor neuron degeneration. In this study, we selectively characterized the expression of miR-9, miR-206, and miR-132 in spinal cord, skeletal muscle, and serum from SMA transgenic mice, and in serum from SMA patients. A systematic analysis of miRNA expression was conducted in SMA mice with different disease severities (severe type I-like and mild type III-like) at different disease stages (pre-, mid-, and late-symptomatic stages), and in morpholino antisense oligonucleotide-treated mice. There was differential expression of all three miRNAs in spinal cord, skeletal muscle and serum samples in SMA mice. Serum miRNAs were altered prior to the changes in spinal cord and skeletal muscle at the presymptomatic stage. The altered miR-132 levels in spinal cord, muscle, and serum transiently reversed to normal level after a single-dose morpholino antisense oligomer PMO25 treatment in SMA mice. We also confirmed a significant alteration of miR-9 and miR-132 level in serum samples from SMA patients. Our study indicates the potential of developing miRNAs as noninvasive biomarkers in SMA.
登录
查看更多内容
影响因子：
46.9
作者：
通讯作者：
--
DOI：
10.1083/jcb.200603008
发表时间：
2006-08-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
通讯作者：
Dutta A
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
DOI：
10.1073/pnas.1015691107
发表时间：
2010-11-23
影响因子：
11.1
作者：
Magill, Stephen T.;Cambronne, Xiaolu A.;Goodman, Richard H.
通讯作者：
Goodman, Richard H.
影响因子：
3.5
作者：
Le Thi Hao;Duy, Phan Q.;Beattie, Christine E.
通讯作者：
Beattie, Christine E.