title: Knockdown of JMJD1C, a target gene of hsa-miR-590-3p, inhibits mitochondrial dysfunction and oxidative stress in MPP+-treated MES23.5 and SH-SY5Y cells.
abstract: MicroRNAs have been shown to be closely related to many neurodegenerative disorders. The present study focuses on the role of hsa-miR-590-3p and its function in Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-590-3p expression in the 1-methyl-4 phenylpyridinium (MPP+)-treated MES23.5 and SH-SY5Y cells. Furthermore, JMJD1C was identified as a target gene of miR-590-3p in humans via the luciferase reporter assay. Our study also demonstrated that up-regulation of miR-590-3p and knockdown of JMJD1C increased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and the downstream targets of PGC-1α, including nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), which are the key genes regulating mitochondrial function. Also, the expression of heme oxygenase-1 (HO-1), NAD (P) H quinone oxidoreductase-1 (NQO-1) and γ-glutamylcysteine synthetase (γ-GCS) involved in anti-oxidation was increased. Moreover, there was a significant increase in the total cellular ATP with an associated decrease in levels of ROS in the absence of JMJD1C. Taken together, these results show that miR-590-3p plays an important role in the pathogenesis of PD, which may be further regarded as a therapeutic target.
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University Department of Neurology Zhengzhou China jinlanwangedu@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University Department of Neurology Zhengzhou China.
authors.forename: T
authors.initials: T
authors.lastname: Le
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University Department of Neurology Zhengzhou China.
authors.forename: R
authors.initials: R
authors.lastname: Wei
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University Department of Neurology Zhengzhou China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiao
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D018384:Oxidative Stress; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010302:Parkinson Disease, Secondary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C568221:MIRN590 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; C520448:JMJD1C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D051547:Heme Oxygenase-1; D010089:Oxidoreductases, N-Demethylating; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005721:Glutamate-Cysteine Ligase; D015655:1-Methyl-4-phenylpyridinium