Choi Insup, Woo Joo Hong, Jou Ilo, Joe Eun-Hye
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.
Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
Exp Neurobiol. 2016 Feb;25(1):14-23. doi: 10.5607/en.2016.25.1.14. Epub 2016 Feb 22.
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.
PTEN诱导的假定激酶1（PINK1）是一种帕金森病（PD）相关基因。我们研究了在脑发育和神经干细胞（NSC）分化过程中受PINK1调控的微小RNA（miRNA），发现1日龄野生型（WT）和PINK1基因敲除（KO）小鼠脑内与肿瘤和炎症相关的miRNA水平存在差异。值得注意的是，与星形胶质瘤相关的miR-326、miR-330和miR-3099在脑发育和NSC分化过程中表达增加，而在缺乏PINK1时显著降低。有趣的是，在睫状神经营养因子（CNTF）存在的情况下，它促使NSC分化为星形胶质细胞，KO NSCs中miR-326、miR-330和miR-3099的水平也低于WT NSCs。此外，这三种miRNA的模拟物在KO NSCs分化过程中增加了星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）的表达，但这些miRNA的抑制剂降低了WT NSCs中GFAP的表达。而且，这些miRNA通过GFAP mRNA的3'-非翻译区（3'-UTR）提高了GFAP的翻译效率。综上所述，这些结果表明PINK1缺乏会降低miR-326、miR-330和miR-3099的表达水平，它们可能在NSC分化和脑发育过程中调节GFAP的表达。
