Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia

• Authors: Anan Xu, Guangzhou Medical University; Rong Li, Guangzhou Medical University; Anbang Ren, Guangzhou Medical University; Haifeng Jian, Guangzhou Medical University; Zhong Huang, Guangzhou Medical University; Qingxing Zeng, Guangzhou Medical University; Baiyao Wang, Guangzhou Medical University; Jieling Zheng, Guangzhou Medical University; Xiaoyu Chen, Guangzhou Medical University; Naiying Zheng, Guangzhou Medical University; Ronghui Zheng, Guangzhou Medical University; Yunhong Tian, Emory University; Mengzhong Liu, Guangzhou Medical University; Zixu Mao, Emory University; Aimin Ji, Guangzhou Medical University; Yawei Yuan, Guangzhou Medical University
• Journal Title: JOURNAL OF NEUROINFLAMMATION
• Volume: Volume 17, Number 1
• Publisher: BMC | 2020-10-28, Pages 321-321
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1186/s12974-020-02001-1
• Subjects: Health Sciences, Immunology; Biology, Neuroscience; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Neurosciences; Neurosciences & Neurology; Microglia; Radiation; Senescence; LncRNA; Inflammation; DNA damage response; Metabolism; INDUCED BRAIN-INJURY; CELLULAR SENESCENCE; DNA-DAMAGE; CELLS; EXPRESSION; DISEASES; STRESS

Abstract

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 the activation of NF-κB/MAPK signaling and subsequent inflammatory cytokine secretion. For the DDR, differential severity of DNA damage altered the expression profiles of RILs. The selected RIL, ENSMUST00000130679, promoted the DDR. For metabolism, blockade of sterol regulatory element-binding protein-mediated lipogenesis attenuated the fold-change of several RILs induced by IR. Conclusions: Our findings revealed that certain RILs interacted with senescence in irradiated microglia. RILs actively participated in the regulation of senescence features, suggesting that RILs could be promising intervention targets to treat RIBI.