miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells

• Published in: Neuroscience bulletin Vol. 32; no. 6; pp. 512 - 522
• Main Authors: Jia, Xiaojian, Wang, Feng, Han, Ying, Geng, Xuewen, Li, Minghua, Shi, Yu, Lu, Lin, Chen, Yun
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.12.2016; Springer
• Subjects: Anatomy; Anesthesiology; Biomedical and Life Sciences; Biomedicine; Cardiac glycosides; Cardiotonic agents; Cell Line, Tumor; Computational Biology; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - genetics; Dopamine Plasma Membrane Transport Proteins - metabolism; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Genetic transcription; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Homeopathy; Human Physiology; Humans; Materia medica and therapeutics; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Minisatellite Repeats - genetics; miRNA; Neuroblastoma - pathology; Neurology; Neurophysiology; Neurosciences; Original; Original Article; Pain Medicine; Phenols; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Therapeutics; Time Factors; Transfection; VNTR; 可变数目串联重复序列; 多巴胺; 神经细胞; 蛋白表达; 负调节; 转运体; 3′-Untranslated region; hsa-miR-137; hsa-miR-491-5p; Variable-number tandem repeat; Dopamine transporter; Solute carrier family 6 member 3; Posttranscriptional regulation
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-016-0061-6

Abstract 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 （3UTR） of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neu- rotransmission. In the present study, we found that miR- 137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine trans- port. 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.