miR-137和miR-491对神经细胞中多巴胺转运体的表达和功能起负向调节作用。
miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells.
作者信息
Jia Xiaojian, Wang Feng, Han Ying, Geng Xuewen, Li Minghua, Shi Yu, Lu Lin, Chen Yun
机构信息
Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.
Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, 453000, China.
出版信息
Neurosci Bull. 2016 Dec;32(6):512-522. doi: 10.1007/s12264-016-0061-6. Epub 2016 Sep 15.
The dopamine transporter (DAT) is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neurotransmission. In the present study, we found that miR-137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine transport. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3'UTR of the DAT and the regulatory effect of miR-491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post-transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.
多巴胺转运体（DAT）参与细胞外多巴胺水平的调节。据报道，DAT的3'非翻译区（3'UTR）中一个40碱基对的可变数目串联重复序列（VNTR）多态性与多巴胺能神经传递异常调节所涉及的各种表型相关。在本研究中，我们发现miR-137和miR-491导致DAT表达显著降低，从而影响神经元多巴胺转运。此外，在DAT沉默后，miR-137和miR-491对这种转运的调节作用消失。位于DAT 3'UTR的VNTR序列上的miR-491种子区域以及miR-491对DAT的调节作用取决于VNTR拷贝数。这些数据表明，miR-137和miR-491在转录后水平调节DAT表达和多巴胺转运，提示microRNA可能成为治疗与DAT功能障碍相关疾病的靶点。
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