Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia

作者：Anan Xu, Rong Li, Anbang Ren, Haifeng Jian, Zhong Huang, Qingxing Zeng, Baiyao Wang, Jieling Zheng, Xiaoyu Chen, Naiying Zheng, Ronghui Zheng, Yunhong Tian, Mengzhong Liu, Zixu Mao, Aimin Ji, Yawei Yuan · 发表于：Journal of Neuroinflammation · 年份：2020 · DOI：10.1186/s12974-020-02001-1 · 被引用次数：16 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Cancer-related molecular mechanisms research、Telomeres, Telomerase, and Senescence

BACKGROUND: Microglia have been implicated in the pathogenesis of radiation-induced brain injury (RIBI), which severely influences the quality of life during long-term survival. Recently, irradiated microglia were speculated to present an aging-like phenotype. Long noncoding RNAs (lncRNAs) have been recognized to regulate a wide spectrum of biological processes, including senescence; however, their potential role in irradiated microglia remains largely uncharacterized. METHODS: We used bioinformatics and experimental methods to identify and analyze the senescence phenotype of irradiated microglia. Western blotting, enzyme-linked immunosorbent assays, immunofluorescence, and quantitative real-time reverse transcription-polymerase chain reaction were performed to clarify the relationship between the radiation-induced differentially expressed lncRNAs (RILs) and the distinctive molecular features of senescence in irradiated microglia. RESULTS: We found that the senescence of microglia could be induced using ionizing radiation (IR). A mutual regulation mode existed between RILs and three main features of the senescence phenotype in irradiated microglia: inflammation, the DNA damage response (DDR), and metabolism. Specifically, for inflammation, the expression of two selected RILs (ENSMUST00000190863 and ENSMUST00000130679) was dependent on the major inflammatory signaling pathways of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). The two RILs modulated...