Dysregulation of miRNAs in patients with Huntington's Disease

Huntington's disease (HD) is a late-onset, progressive, neurodegenerative disorder, usually in the second decade of life, with a fatal outcome in about 6 to 20 years after onset. Many studies have focused on the dysregulation of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), which play a regulatory function on messenger RNAs (mRNAs) by degrading or inhibiting them. Since abnormal gene expression underlies many diseases, miRNAs are thought to exert influence on several aspects. Differential expression analysis was conducted on patient vs. control samples using the Bioconductor DESeq2 package. Instead, to perform miRNA-target analysis, clusterProfiler was used to study functional target analysis. Specifically, clusterProfiler analysis was based on Gene Ontology (GO - Cellular Component (CC), Biological Process (BP) and Molecular Function (MF)) and KEGG pathway database, selecting a set of miRNAs with padj=0.05 and |fold-change|=1.5. Differential expression analysis between the two groups revealed 270 miRNAs were significantly upregulated (fold change = 1.5), while 519 were significantly downregulated (fold change = -1.5). The enrichment analysis allowed us to identify a large number of functional terms associated with the target genes of dysregulated miRNAs. In particular, among the terms we focused on: positive regulation of cell development and nucleocytoplasmic transport, vacuolar membrane and chromosome, centromeric region and, finally DNA-binding transcription factor binding and nuclear receptor binding.