Abstract Details

Title Down-Regulation of DICER1 Leading to Abnormal Expression of Mature microRNAs and NEUROG2 Is Involved with Aberrant Neuroglial Differentiation in Focal Cortical Dysplasias (FCD)

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S08 - (-)

Poster/Presentation
Number 002

Objective

Background FCD is characterized by a spectrum of abnormalities in the development of the laminar structure of the human cerebral cortex. Microscopically, FCD is usually associated with cell abnormalities, giant/dysmorphic neurons and balloon cells. The tissue is highly epileptogenic and the mechanism underlying the development of FCD is poorly understood. MicroRNAs are small noncoding RNAs which regulate gene expression.

Design/Methods We used total RNA isolated from tissue obtained after surgery performed in 17 patients with type II FCD and 20 controls from autopsy. MiRNA expression profile was assessed by Affymetrix GeneChip platform miRNA array. Quantitative PCR (qPCR) was used to validate miRNAs and target genes.

Results Microarray revealed 39 microRNAs which were downregulated and only one was overexpressed. Decreased expression of three miRNAs was confirmed by qPCR: hsa-miR-31, hsa-miR34a and hsa-let-7f. In addition, we found that NEUROG2, a possible target gene regulated by hsa-miR-31 is over expressed in FCD tissue. In addition, we observed downregulation of DICER1.

Conclusions Since DICER1 is an important element in the biogenesis of microRNAs, its downregulation could be the key initial event leading to the substantial downregulation of microRNAs we found in FCD. Furthermore, the three microRNAs confirmed to be downregulated in FCD are known to be tumor suppressors; therefore, they may be leading to the aberrant histopathological features, seen in FCD type II, such as dysmorphic and giant neurons. In addition, our finding of overexpression of NEUROG2, may lead to failure in the transition between neurogenesis and gliogenesis and could explain the existence of immature or poorly differentiated cell types, such as balloon cells, which is typical of FCD type II.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Danyella Dogini, PhD	No disclosure on file
	No disclosure on file
Ana C. Coan, MD (Unicamp)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Steven Galetta, MD, FAAN (NYU Langone Medical Center)	Dr. Galetta has nothing to disclose.
	No disclosure on file
	No disclosure on file
Fernando Cendes, MD, PhD, FAAN (Departamento de Neurologia; FCM; UNICAMP)	Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for United Medical – Brazil. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zodiac Pharma . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma – Brazil . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology - Epilepsy. The institution of Dr. Cendes has received research support from São Paulo Research Foundation - FAPESP. The institution of Dr. Cendes has received research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil . The institution of Dr. Cendes has received research support from NIH.
Iscia Lopes-Cendes, MD, PhD (University of Campinas - UNICAMP)	No disclosure on file

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