EVIDENCE OF MICRORNA REGULATION IN MESIAL TEMPORAL SCLEROSIS
Abstract number :
2.324
Submission category :
11. Human Genetics
Year :
2009
Submission ID :
10033
Source :
www.aesnet.org
Presentation date :
12/4/2009 12:00:00 AM
Published date :
Aug 26, 2009, 08:12 AM
Authors :
Danyella Dogini, T. Pereira, C. Rocha, C. Yasuda, H. Tedeschi, E. de Oliveira, C. Maurer-Morelli, F. Cendes and I. Lopes-Cendes
Rationale: microRNAs are a new class of small RNA molecules (21-24 nucleotide-long) that negatively regulate gene expression either by translational repression or target mRNA degradation. It is believed that about 30% of all human genes are targeted by these molecules. miRNAs are involved in many important biological processes including cell differentiation, embryonic development and central nervous system formation. We carried out the present study in order to investigate the possible role of miRNA regulation in the biological processes occurring in mesial temporal sclerosis (MTS). Methods: Total RNA was isolated with Trizol of hippocampal tissue from 4 patients who underwent selective resection of the mesial temporal structures for the treatment of clinically refractory seizures. In addition we used control samples from autopsy (n=4) for comparison. RNA samples were used in real-time PCR reactions with TaqMan™ MicroRNA assays (Applied Biosystems) to quantify 157 miRNAs in human hippocampal tissue. Results: Bioinformatics analyzes identified three miRNAs species which were differently expressed in patients as compared to controls: let7a was over expressed in patients (4 fold increased), miR-29b and miR-30d were down- regulated in patients (2.5 fold and 0.5 fold decreased, respectively). Possible target genes for let-7a are NME6 and NCAM1 (which would be down-regulated in patients); for miR-29b is MCL-1 and for miR30d are CTNND2, LGI1 and SON (which would be up-regulated in patients). Conclusions: We have identified three miRNA species differently expressed in MTS. Gene functions related to the possible miRNA targets are involved mainly with cell proliferation, neurogenesis, cell adhesion and apoptosis. Our results reveal new targets which should be explored in additional studies addressing miRNA regulation in MTS.
Genetics