Zhao Ye, Lu Congxia, Wang Huiling, Lin Qing, Cai Liangliang, Meng Fanrong, Tesfaye Enque Biniam, Lai Hsin-Chih, Tzeng Chi-Meng
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China.
Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture, Nanjing Tech University, Nanjing 211800, China.
Mol Ther Methods Clin Dev. 2020 Oct 14;19:398-410. doi: 10.1016/j.omtm.2020.10.005. eCollection 2020 Dec 11.
Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miRNAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor κB (NF-κB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting for human EUE.
癫痫在全球约影响7000万人,病因不明的比例为65%。这一比例的癫痫被称为病因不明的癫痫(EUE)。人们认识到微小RNA(miRNA)失调会导致包括癫痫在内的精神障碍。然而,在EUE中对miRNA失调的了解甚少。在这里,我们通过微阵列技术对EUE进行了miRNA表达谱分析,并鉴定出57个具有显著致病性变化的miRNA。数据和生物信息学分析结果表明,在这些miRNA中,hsa-微RNA(miR)-1275与神经疾病高度相关。随后,收集了新的血清和脑脊液样本,通过TaqMan检测法验证hsa-miR-1275的表达。结果显示,EUE血清中的hsa-miR-1275显著增加,但在脑脊液中,该miRNA减少。此外,根据靶标预测工具和基因本体分析,选择该基因作为hsa-miR-1275的靶标。验证试验证明,hsa-miR-1275可特异性抑制MECP2的表达。此外,hsa-miR-1275的过表达可提高核因子κB(NF-κB)的表达并促进细胞凋亡。综上所述,hsa-miR-1275可能是人类EUE的一种新型生物标志物靶点。