Mechanism(s) of Alteration of Micro RNA Expressions in Huntington's Disease and Their Possible Contributions to the Observed Cellular and Molecular Dysfunctions in the Disease

To identify the mechanism of deregulation of micro RNAs (miRNAs) altered in Huntington's disease (HD) and their possible contributions to the altered cellular and molecular functions observed in the disease, we analyzed the altered miRNAs in the postmortem brains of HD patients. There are 54 miRNAs differentially expressed in HD brains of which 30 are upregulated and 24 downregulated. Some of these miRNAs were also altered in various models of the disease. Regulation of these miRNAs was attributed to transcription factors and the host genes to which these miRNAs reside. We observed that transcription regulators TP53, E2F1, REST, and GATA4 together could regulate expressions of 26 miRNAs in HD. Altered expressions of 13 intronic miRNAs were correlated with the expressions of their host genes. From literature, we further collected 287 experimentally validated targets of miRNAs upregulated in HD, while 304 validated targets of downregulated miRNAs in HD. Analysis of these validated target genes of altered miRNAs by gene ontology (GO) revealed that these genes are significantly enriched in GO terms belonging to (1) apoptosis, (2) differentiation and development, (3) fatty acid, cholesterol, lipid, glucose, and carbohydrate metabolism, (4) cell cycle and growth, and (5) transcription regulation. Experimental evidences that these processes are altered in HD are provided from published reports. In conclusion, altered miRNAs in HD might target many genes and may contribute to the altered cellular and molecular functions observed in HD.