MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis

Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance (FDR q-value

长期以来，转录失调被认为是亨廷顿病（Huntington's disease, HD）发病机制的核心。微小RNA（MicroRNAs, miRNAs）是一类主要的转录后调控系统，可通过阻断翻译起始或靶向转录本进行储存或降解来发挥调控作用。本研究采用下一代微小RNA测序技术，对12例亨廷顿病患者与9例对照者的前额叶皮层（布罗德曼9区，Brodmann Area 9）样本进行检测，最终鉴定出5个在亨廷顿病样本中达到全基因组显著性水平的上调微小RNA（miR-10b-5p、miR-196a-5p、miR-196b-5p、miR-615-3p及miR-1247-5p），其错误发现率q值（FDR q-value）