College of Economy and Management, Changzhou Institute of Technology, Changzhou, Jiangsu, China (mainland).
Department of Health, Changzhou Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Changzhou, Jiangsu, China (mainland).
Med Sci Monit. 2018 Jun 29;24:4465-4473. doi: 10.12659/MSM.908543.
BACKGROUND Major depressive disorder (MDD) is a chronic, life-threatening, highly disabling disease. Standardized treatment with fewer adverse effects, quick onset, and long-term maintenance of the effects of brief treatment for MDD is always being pursued. Long non-coding RNAs (lncRNAs) are highly expressed in the central nervous system and are involved in the occurrence and development of neurodegenerative and psychiatric diseases. This study aimed to investigate whether the overexpression and interference of 3 differentially down-regulated lncRNAs (NONHSAT142707, NONHSAG045500, and ENST00000517573) in MDD can affect the expression of central neurotransmitter serotonin (5-hydroxytryptamine) transporter (SERT) in vitro. MATERIAL AND METHODS First, we synthesized and validated the effect of 3 lncRNA plasmids and small interfering RNAs (siRNAs); next, we transfected the plasmids and siRNAs that caused significant overexpression or interference in SK-N-SH cells, and tested the expression of SERT by qRT-PCR. RESULTS The results showed that 3 lncRNA plasmids and siRNAs2 caused overexpression and interference, respectively. Only the overexpression of NONHSAG045500 could significantly inhibit the expression of SERT; interference with NONHSAG045500 could significantly strengthen the expression of SERT. CONCLUSIONS This study indicated that the expression of SERT could be regulated by up-regulating or down-regulating NONHSAG045500 expression and suggested that NONHSAG045500 could potentially be established as a new therapeutic target of MDD. Future work may be needed to definitively determine the correlation between NONHSAG045500 and SERT in vivo.
重度抑郁症（MDD）是一种慢性、危及生命、高度致残的疾病。人们一直在寻求标准治疗方法，以减少不良反应、快速起效，并长期维持 MDD 短期治疗的效果。长链非编码 RNA（lncRNA）在中枢神经系统中高度表达，参与神经退行性和精神疾病的发生和发展。本研究旨在探讨 MDD 中 3 种差异下调的 lncRNA（NONHSAT142707、NONHSAG045500 和 ENST00000517573）的过表达和干扰是否会影响中枢神经递质 5-羟色胺（5-HT）转运体（SERT）的表达。
首先，我们合成并验证了 3 种 lncRNA 质粒和小干扰 RNA（siRNA）的作用；然后，我们转染了在 SK-N-SH 细胞中引起显著过表达或干扰的质粒和 siRNA，并用 qRT-PCR 检测 SERT 的表达。
结果表明，3 种 lncRNA 质粒和 siRNA2 分别引起过表达和干扰。只有 NONHSAG045500 的过表达才能显著抑制 SERT 的表达；干扰 NONHSAG045500 可显著增强 SERT 的表达。
本研究表明，SERT 的表达可通过上调或下调 NONHSAG045500 的表达来调节，并提示 NONHSAG045500 可能成为 MDD 的新治疗靶点。未来的工作可能需要明确确定 NONHSAG045500 与 SERT 之间的体内相关性。
