title: Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.
abstract: The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells), an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination) in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy; Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchini
authors.affiliation: Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Section of Pathology, Bellaria Hospital, Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Marucci
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, University of Ferrara, Ferrara, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Paradiso
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, University of Ferrara, Ferrara, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Roncon
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; Ri.MED Foundation, Palermo, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Cifelli
authors.affiliation: Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy; Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Ferrara, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: IRCCS Institute of Neurological Sciences, Section of Neurosurgery, Bellaria Hospital, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giulioni
authors.affiliation: IRCCS Institute of Neurological Sciences, Section of Neurology, Bellaria Hospital, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Michelucci
authors.affiliation: IRCCS Institute of Neurological Sciences, Section of Neurology, Bellaria Hospital, Bologna, Italy; Danish Epilepsy Center, Epilepsihospital, Dianalund, Denmark.
authors.forename: Guido
authors.initials: G
authors.lastname: Rubboli
authors.affiliation: Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Ferrara, Italy; National Institute of Neuroscience, Torino, Italy; Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Simonato
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D004351:Drug Resistance; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics
chemical_list: C473287:ANTXR1 protein, human; C568526:MIRN487 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface