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

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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 (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.

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Acknowledgments

This work was supported by grants from the National Postdoctoral Science Foundation, China (2014M552219), the Natural Science Foundation of Guangdong Province, China (2015A030313889, 2015A030401013, 2014A030313709, and 2014A030313710), the Science and Technology Planning Project of Shenzhen Municipality, China (ZDSYS201504301045406, JCYJ20150403110829621, JCYJ20150403091443301, JCYJ20140415162542975, JCYJ20140415162338855, JCYJ20140828163634004, and JCYJ20120616144352139), and the Health and Family Planning Commission Project of Shenzhen Municipality, China (201401026).

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Authors and Affiliations

  1. 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

    Xiaojian Jia, Feng Wang, Xuewen Geng, Minghua Li, Yu Shi & Yun Chen

  2. Institute of Mental Health, Peking University Sixth Hospital and Key Laboratory of Mental Health, National Institute on Drug Dependence, Peking University, Beijing, 100191, China

    Ying Han & Lin Lu

  3. Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, 453000, China

    Feng Wang

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  1. Xiaojian Jia
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  2. Feng Wang
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Correspondence to Lin Lu or Yun Chen.

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Jia, X., Wang, F., Han, Y. et al. miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells. Neurosci. Bull. 32, 512–522 (2016). https://doi.org/10.1007/s12264-016-0061-6

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