title: Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson's Disease via Regulation of Its Target Gene TRPM7.
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.
authors.affiliation: Department of Neurology, Cangzhou Central Hospital , Cangzhou, 061001, China.
authors.forename: Chao Ping
authors.initials: CP
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Cangzhou Medical College, Guangzhou Road No. 1, Cangzhou, 061001, China. zhenhuazhangcz@tom.com.
authors.forename: Zhen Hua
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Cangzhou Central Hospital , Cangzhou, 061001, China.
authors.forename: Li Hua
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Cangzhou Central Hospital , Cangzhou, 061001, China.
authors.forename: Han Chen
authors.initials: HC
authors.lastname: Rui
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C580892:MIRN22 microRNA, rat; D035683:MicroRNAs; D050053:TRPM Cation Channels; D016627:Oxidopamine; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human
keywords: MicroRNAs; Parkinson’s disease; TRPM7; miR-22