Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines

• Published in: PloS one 2016-10, Vol.11 (10), p.e0164425-e0164425
• Main Authors: Mundalil Vasu, Mahesh, Anitha, Ayyappan, Takahashi, Taro, Thanseem, Ismail, Iwata, Keiko, Asakawa, Tetsuya, Suzuki, Katsuaki
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Biology and life sciences; Biotechnology; Brain; Brain research; Cancer; Cell culture; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line, Tumor; Cell lines; Cell Survival - drug effects; Cell Survival - genetics; Child & adolescent psychiatry; Drugs; Fluoxetine; Fluoxetine - pharmacology; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Genes; Humans; Kinases; Medicine; MicroRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - genetics; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - genetics; Neurons; Neurophysiology; Neuroprotection; Neurosciences; Proteins; Psychotropic drugs; Research and Analysis Methods; Serotonin; Serotonin uptake inhibitors; Social Sciences; Up-Regulation - drug effects; Up-Regulation - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0164425

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.