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Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease via Regulation of Its Target Gene TRPM7

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Abstract

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder with only symptomatic treatment available, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Ample evidence indicated that microRNAs (miRs) could regulate post-transcriptional gene expression and neuronal disease. In the present study, we have evaluated the effects and mechanism of miR-22 in PC12 pheochromocytoma cells treated with 6-hydroxydopamine (6-OHDA) to mimic PD. RT-PCR results showed that the expression of miR-22 is downregulated in 6-OHDA-treated PC12 cells, and the overexpression of miR-22 significantly promoted the survival and proliferation of 6-OHDA-induced PC12 cells, whereas miR-22 inhibitor reversed these effects. In addition, PC12 cells were treated with miR-22 mimics or inhibitor following 6-OHDA administration, which medicated ROS production and upregulation or downregulation of caspase-3 activity, respectively. A luciferase reporter assay revealed that transient receptor potential melastatin 7 (TRPM7) is a direct target gene of miR-22, and miR-22 overexpression markedly downregulated the level of TRPM7. Strikingly, further analysis showed that miR-22 mediated 6-OHDA-induced PC12 cell survival and proliferation by targeting TRPM7. Taken together, the present study showed that miR-22 overexpression exhibited neuroprotective and reversal effects on the 6-OHDA-induced PC12 cell growth and apoptosis by targeting TRPM7.

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Authors and Affiliations

  1. Department of Neurology, Cangzhou Central Hospital , Cangzhou, 061001, China

    Chao Ping Yang, Li Hua Zhang & Han Chen Rui

  2. Department of Internal Medicine, Cangzhou Medical College, Guangzhou Road No. 1, Cangzhou, 061001, China

    Zhen Hua Zhang

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  1. Chao Ping Yang
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  2. Zhen Hua Zhang
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  3. Li Hua Zhang
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  4. Han Chen Rui
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Correspondence to Zhen Hua Zhang.

Electronic Supplementary Material

Supplementary fig 1

miR-22 overexpression reversed the effects of 6-OHDA on SH-SY5Y cell survival and proliferation. (A) miR-22 significantly increased 6-OHDA (100 μM) induced SH-SY5Y cell death. Cell viability was measured by MTT assay; (B) PC12 cell proliferation was measured by CCK-8 assay. Experiments were repeated three times. Data are presented as mean ± SD, N = 3. * P < 0.05 vs control, # P < 0.05 vs 6-OHDA group. (GIF 70 kb)

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Yang, C.P., Zhang, Z.H., Zhang, L.H. et al. Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson’s Disease via Regulation of Its Target Gene TRPM7. J Mol Neurosci 60, 445–452 (2016). https://doi.org/10.1007/s12031-016-0828-2

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  • DOI: https://doi.org/10.1007/s12031-016-0828-2

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