title: MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction.
abstract: MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neurodegenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, β-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.
authors.affiliation: No. 2 Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001, China .
authors.forename: Kuo
authors.initials: K
authors.lastname: Li
authors.affiliation: No. 2 Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001, China .
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: No. 2 Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001, China .
authors.forename: Chunxue
authors.initials: C
authors.lastname: Ji
authors.affiliation: No. 2 Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001, China .
authors.forename: Lixuan
authors.initials: L
authors.lastname: Wang
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C499631:TFAM protein, human; D014157:Transcription Factors; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: Parkinson’s disease; amyloid precursor protein; hsa-miR-144-3p; mitochondrial functions