Abstract：
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder due to deletion or mutation of survival motor neuron 1 (SMN1) gene. Although survival motor neuron 2 (SMN2) gene is still present in SMA patients, the production of full-length survival motor neuron (SMN) protein is insufficient owing to missing or mutated SMN1. No current disease-modifying therapies can cure SMA. The aim of this study was to explore microRNA (miRNA)-based therapies that may serve as a potential target for therapeutic intervention in delaying SMA progression or as treatment. The study screened for potentially dysregulated miRNAs in SMA fibroblast-derived iPSCs using miRNA microarray. Results from the miRNA microarray were validated using quantitative reverse transcription polymerase chain reaction. Bioinformatics analysis using various databases was performed to predict the potential putative gene targeted by hsa-miR-663a. The findings showed differential expression of hsa-miR-663a in SMA patients in relation to a healthy control. Bioinformatics analysis identified GNG7, IGF2, and TNN genes that were targeted by hsa-miR-663a to be involved in the PI3K-AKT pathway, which may be associated with disease progression in SMA. Thus, this study suggests the potential role of hsa-miR-663a as therapeutic target for the treatment of SMA patients in the near future.
摘要：
脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传性神经肌肉疾病，是由于存活运动神经元1（SMN1）基因的缺失或突变所致。尽管存活运动神经元2（SMN2）基因仍然存在于SMA患者中，由于SMN1缺失或突变，全长存活运动神经元（SMN）蛋白的产生不足。目前没有疾病改善疗法可以治愈SMA。这项研究的目的是探索基于microRNA（miRNA）的疗法，这些疗法可以作为延迟SMA进展或治疗的治疗干预的潜在靶标。该研究使用miRNA微阵列筛选了SMA成纤维细胞来源的iPSC中潜在失调的miRNA。使用定量逆转录聚合酶链反应验证来自miRNA微阵列的结果。使用各种数据库进行生物信息学分析以预测hsa-miR-663a靶向的潜在推定基因。结果显示SMA患者中hsa-miR-663a的差异表达与健康对照有关。生物信息学分析确定了GNG7，IGF2和TNN基因被hsa-miR-663a靶向参与PI3K-AKT途径，这可能与SMA的疾病进展有关。因此，本研究提示hsa-miR-663a作为SMA患者近期治疗靶点的潜在作用.
