Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 45, Issue 2, Pages 441-450Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2019.4426
Keywords
miRNA-384-5p; Parkinson's disease; Sirtuin 1
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Funding
- Science and Technology Plan of Shaanxi Provincial Health Planning Commission [2016D065]
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Parkinson's disease (PD) is the second most common neurodegenerative disorder. miR-384-5p expression has been shown to be increased in an in vitro model of PD; however, it remains unknown whether there are other molecules that can be regulated by miR-384-5p in in vivo and in vitro models of PD; thus, the present study aimed to elucidate this matter. Rotenone was applied for the establishment of in vitro and in vivo models of PD in the present study. Motor disability and equilibrium were determined by a swimming test and traction test, respectively. mRNA and protein levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The association between miR-384-5p and Sirtuin 1 (SIRT1) expression was verified by dual luciferase reporter assay. The alpha-synuclein aggregation was evaluated by immunofluorescence. The results from the in vitro model of PD demonstrated that, the mice in the PD group exhibited decreased scores in the swimming test and traction test, which were accompanied by increased alpha-synuclein aggregation. In addition, the expression of miR-384-5p, which targeted the 3'untranslated region (3'UTR) of SIRT1, was verified to be increased in mice and SH-SY5Y cells in the PD group, whereas SIRT1 exhibited the opposite changes. Moreover, increased mRNA and protein levels of p53 and FOXO1 were observed in mice and SH-SY5Y cells in the PD group. In addition, the SH-SY5Y cells in the PD group exhibited a higher cell apoptotic rate. On the whole, the findings of this study demonstrate that miRNA-384-5p promotes the progression of PD by targeting SIRT1.
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