Guo Yawei, Hong Wenming, Wang Xinming, Zhang Pengying, Körner Heinrich, Tu Jiajie, Wei Wei
Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology, Anhui Medical University, Ministry of Education, Hefei, China.
Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Mol Neurosci. 2019 May 10;12:125. doi: 10.3389/fnmol.2019.00125. eCollection 2019.
The essential roles of microglia in maintaining homeostasis in the healthy brain and contributing to neuropathology are well documented. Emerging evidence suggests that epigenetic modulation regulates microglial behavior in both physiological and pathological conditions. MicroRNAs (miRNAs) are short, non-coding epigenetic regulators that repress target gene expression mostly binding to 3'-untranslated region (3'-UTR) of mRNA in a Dicer-dependent manner. Dysregulation of certain miRNAs can contribute to microglial hyper-activation, persistent neuroinflammation, and abnormal macrophage polarization in the brain. These abnormal conditions can support the pathogenesis of neurological disorders such as glioma, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), stroke, ischemia, and spinal cord injury (SCI). However, the roles of miRNAs in microglia in health and neurological disease have not been systematically summarized. This review will first report the role of Dicer, a key endoribonulease that is responsible for most miRNA biogenesis in microglia. Second, we will focus on recent research about the function of miRNAs in activation, inflammation and polarization of microglia, respectively. In addition, potential crosstalk between microglia and glioma cells miRNAs will be discussed in this part. Finally, the role of two essential miRNAs, miR-124, and miR-155, in microglia will be highlighted.
小胶质细胞在维持健康大脑的内环境稳定以及导致神经病理学方面的重要作用已有充分记载。新出现的证据表明,表观遗传调控在生理和病理条件下均调节小胶质细胞的行为。微小RNA(miRNA)是短的非编码表观遗传调节因子,主要以Dicer依赖的方式与mRNA的3'非翻译区(3'-UTR)结合来抑制靶基因表达。某些miRNA的失调可导致小胶质细胞过度激活、持续性神经炎症以及大脑中异常的巨噬细胞极化。这些异常情况可支持神经疾病如胶质瘤、阿尔茨海默病(AD)、肌萎缩侧索硬化症(ALS)、中风、缺血和脊髓损伤(SCI)的发病机制。然而,miRNA在健康和神经疾病中小胶质细胞中的作用尚未得到系统总结。本综述将首先报道Dicer的作用,Dicer是一种关键的核糖核酸内切酶,负责小胶质细胞中大多数miRNA的生物合成。其次,我们将分别关注关于miRNA在小胶质细胞激活、炎症和极化功能方面的最新研究。此外,本部分还将讨论小胶质细胞与胶质瘤细胞之间潜在的miRNA相互作用。最后,将重点介绍两种重要miRNA,即miR-124和miR-155在小胶质细胞中的作用。