Regulatory coupling between long noncoding RNAs and senescence in irradiated microglia

Journal of Neuroinflammation

Zixu Mao¹  Anan Xu²  Anbang Ren²  Yawei Yuan²  Xiaoyu Chen²  Aimin Ji²  Haifeng Jian²  Zhong Huang²  Rong Li²  Baiyao Wang²  Ronghui Zheng²  Qingxing Zeng²  Yunhong Tian²  Jieling Zheng²  Naiying Zheng²  Mengzhong Liu³ 

[1] Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA;Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No 78, Hengzhigang Road, Yuexiu District, 510095, Guangzhou, Guangdong, People’s Republic of China;Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No 78, Hengzhigang Road, Yuexiu District, 510095, Guangzhou, Guangdong, People’s Republic of China;Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China;

关键词: Microglia;    Radiation;    Senescence;    LncRNA;    Inflammation;    DNA damage response;    Metabolism;   

DOI  :  10.1186/s12974-020-02001-1

来源: Springer

【 摘 要 】

BackgroundMicroglia 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY