title: PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation.
abstract: PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development.
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Insup
authors.initials: I
authors.lastname: Choi
authors.affiliation: Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Joo Hong
authors.initials: JH
authors.lastname: Woo
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.; Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.affiliation: Neuroscience Graduate Program Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.; Department of Pharmacology, Ajou University School of Medicine, Suwon 16499, Korea.; Department of Brain Science, Ajou University School of Medicine, Suwon 16499, Korea.; Brain Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Joe
keywords: PINK1; Parkinson's disease; miR-3099; miR-326; miR-330