title: Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines.
abstract: Evidence suggests neuroprotective effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on the developed neurons in the adult brain. In contrast, the drug may be deleterious to immature or undifferentiated neural cells, although the mechanism is unclear. Recent investigations have suggested that microRNAs (miRNA) may be critical for effectiveness of psychotropic drugs including SSRI. We investigated whether fluoxetine could modulate expressions of neurologically relevant miRNAs in two neuroblastoma SK-N-SH and SH-SY5Y cell lines. Initial screening results revealed that three (miR-489, miR-572 and miR-663a) and four (miR-320a, miR-489, miR-572 and miR-663a) miRNAs were up-regulated in SK-N-SH cells and SH-SY5Y cells, respectively, after 24 hours treatment of fluoxetine (1-25 μM). Cell viability was reduced according to the dose of fluoxetine. The upregulation of miR-572 and miR-663a was consistent in both the SH-SY5Y and SK-N-SH cells, confirmed by a larger scale culture condition. Our data is the first in vitro evidence that fluoxetine could increase the expression of miRNAs in undifferentiated neural cells, and that putative target genes of those miRNAs have been shown to be involved in fundamental neurodevelopmental processes.
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mundalil Vasu
authors.affiliation: Department of Neurogenetics, Institute for Communicative and Cognitive Neurosciences (ICCONS), Kerala, India.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.affiliation: Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Neurogenetics, Institute for Communicative and Cognitive Neurosciences (ICCONS), Kerala, India.
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.affiliation: Research Center for Child Mental Development, University of Fukui, Fukui, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Asakawa
authors.affiliation: Department of Biofunctional Imaging, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics*; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C000603872:MIRN-572 microRNA, human; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D005473:Fluoxetine