title: Niemann-Pick type C fibroblasts have a distinct microRNA profile related to lipid metabolism and certain cellular components.
abstract: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at post-transcriptional level. Dysregulation of miRNA expression may lead to severe pathophysiologies in human cells. Niemann-Pick type C (NPC) disease is a complex lipid storage disease characterized by late endosomal-lysosomal accumulation of multiple lipid molecules. Our aim was to characterize the miRNA profile in NPC fibroblasts as they may play an active role in the NPC disease associated changes in the cellular physiology. To investigate the miRNA expression, total RNAs were isolated from cultured human NPC fibroblasts and healthy fibroblasts and then, TaqMan Low-Density Array system containing 365 mature human miRNAs was used. Expression differences between the healthy and NPC cells were detected according to the relative quantification values. Target genes were predicted by using three different algorithms and classified regarding NPC related biological processes and cellular components. We found that three miRNAs, miR-196a, miR-196b and miR-296 were up-regulated (>3.5-fold increase, p<0.05) whereas 38 miRNAs were significantly down-regulated in NPC cells (>3.5-fold decrease, p<0.05). Among these non-coding RNAs, miR-98 was the most down-regulated (-33.3-fold) miRNA and miR-143, the lipid biosynthesis associated miRNA, had a 20-fold decreased expression in the NPC cells. Additionally, gene ontology analyses of the target genes suggested a distinct role for each miRNA. Our results show that NPC fibroblasts have an altered miRNA expression profile and certain miRNAs have importance in disease pathogenesis as well as the therapeutic capacity to correct lipid related pathophysiologies in the NPC cells.
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital and University of Tampere, Finland. ozsaitb@istanbul.edu.tr
authors.forename: Bilge
authors.initials: B
authors.lastname: Ozsait
authors.forename: Evrim
authors.initials: E
authors.lastname: Komurcu-Bayrak
authors.forename: Mari
authors.initials: M
authors.lastname: Levula
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Myriam
authors.initials: M
authors.lastname: Rai
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
mesh_terms: D015536:Down-Regulation; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis*; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism*
chemical_list: D035683:MicroRNAs