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

Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines.
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DOI:
10.1371/journal.pone.0164425
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Suzuki K
Suzuki K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mundalil Vasu M;Anitha A;Takahashi T;Thanseem I;Iwata K;Asakawa T;Suzuki K

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有证据表明氟西汀(一种选择性血清素再摄取抑制剂 (SSRI))对成人大脑中发育的神经元具有神经保护作用。相反,该药物可能对未成熟或未分化的神经细胞有害,尽管其机制尚不清楚。最近的研究表明,微小 RNA (miRNA) 可能对包括 SSRI 在内的精神药物的有效性至关重要。我们研究了氟西汀是否可以调节两种神经母细胞瘤 SK-N-SH 和 SH-SY5Y 细胞系中神经相关 miRNA 的表达。初步筛选结果显示,氟西汀(1-25 μM)处理 24 小时后,SK-N-SH 细胞和 SH-SY5Y 细胞中分别有 3 个(miR-489、miR-572 和 miR-663a)和 4 个(miR-320a、miR-489、miR-572 和 miR-663a)miRNA 上调。根据氟西汀的剂量,细胞活力降低。更大规模的培养条件证实了 miR-572 和 miR-663a 的上调在 SH-SY5Y 和 SK-N-SH 细胞中是一致的。我们的数据是第一个体外证据,证明氟西汀可以增加未分化神经细胞中 miRNA 的表达,并且这些 miRNA 的假定靶基因已被证明参与基本的神经发育过程。
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.
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