Differential DNA Methylation of MicroRNA Genes in Temporal Cortex from Alzheimer's Disease Individuals

Author(s)

Villela, Darine ; Ramalho, Rodrigo F. ; Silva, Aderbal R. T. ; Brentani, Helena ; Suemoto, Claudia K. ; Pasqualucci, Carlos Augusto ; Grinberg, Lea T. ; Krepischi, Ana C. V. ; Rosenberg, Carla

• Document type: Journal article
• Source: NEURAL PLASTICITY; v. 2016, p. 10-pg., 2016-01-01.

Abstract

This study investigated for the first time the genomewide DNA methylation changes of noncoding RNA genes in the temporal cortex samples from individuals with Alzheimer's disease (AD). The methylome of 10 AD individuals and 10 age-matched controls were obtained using Illumina 450K methylation array. A total of 2,095 among the 15,258 interrogated noncoding RNA CpG sites presented differential methylation, 161 of which were associated with miRNA genes. In particular, 10 miRNA CpG sites that were found to be hypermethylated in AD compared to control brains represent transcripts that have been previously associated with the disease. This miRNA set is predicted to target 33 coding genes from the neuregulin receptor complex (ErbB) signaling pathway, which is required for the neurons myelination process. For 6 of these miRNA genes (MIR9-1, MIR9-3, MIR181C, MIR124-1, MIR146B, and MIR451), the hypermethylation pattern is in agreement with previous results from literature that shows downregulation of miR-9, miR-181c, miR-124, miR-146b, and miR-451 in the AD brain. Our data implicate dysregulation of miRNA methylation as contributor to the pathogenesis of AD. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes
• Grantee: Carla Rosenberg
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/15503-0 - Genomic imbalances on the anatomopathological and cognitive manifestations of Alzheimer’s Disease
• Grantee: Darine Christina Maia Villela
• Support Opportunities: Scholarships in Brazil - Doctorate