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LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1 alpha-FOXO4-p21-dependent signaling axis

文献类型：期刊论文

作者Sun, Xuedan5,6; Thorne, Rick Francis7,8; Zhang, Xu Dong7,9; He, Miao2; Li, Jinming7; Feng, Shanshan3; Liu, Xiaoying4,7; Wu, Mian1,5,6,7
刊名EMBO REPORTS
出版日期2020-04-03
卷号21
关键词cellular senescence GUARDIN lncRNAs LRP130-PGC1 alpha p21
ISSN号1469-221X
DOI10.15252/embr.201948796
通讯作者Feng, Shanshan(fengss2000@126.com) ; Liu, Xiaoying(liuxiaoying@ahmu.edu.cn) ; Wu, Mian(wumian@ustc.edu.cn)
英文摘要The long noncoding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions toward senescence or apoptosis, but the underlying molecular signals are unknown. Here, we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1 alpha. GUARDIN acts as a scaffold to stabilize LRP130/PGC1 alpha heterodimers and their occupancy at the FOXO4 promotor. Destabilizing this complex by silencing of GUARDIN, LRP130, or PGC1 alpha leads to increased expression of FOXO4 and upregulation of its target gene p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, an agent that suppresses cell senescence. FOS-like antigen 2 (FOSL2) acts as a transcriptional repressor of GUARDIN, and lower FOSL2 levels in response to rapamycin correlate with increased levels of GUARDIN. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1 alpha-FOXO4 signaling axis, and moreover, GUARDIN contributes to the anti-aging activities of rapamycin.
WOS关键词LONG NONCODING RNA ; RAPAMYCIN ; MECHANISMS ; EXPRESSION ; LRPPRC ; CANCER ; CELLS ; P21(WAF1/CIP1) ; HOMEOSTASIS ; METABOLISM
资助项目National Key R&D Program of China[2018YFA0107100] ; National Natural Science Foundation of China[81820108021] ; National Natural Science Foundation of China[31871437] ; National Natural Science Foundation of China[31601146] ; National Natural Science Foundation of China[81772908] ; National Natural Science Foundation of China[81970153] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; National Health and Medical Research Council of Australia[1147271]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
WOS记录号WOS:000524354400004
出版者WILEY
资助机构National Key R&D Program of China ; National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Health and Medical Research Council of Australia
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/103673]  
专题中国科学院合肥物质科学研究院
通讯作者Feng, Shanshan; Liu, Xiaoying; Wu, Mian
作者单位1.Henan Univ, Key Lab Stem Cell Differentiat & Modificat, Sch Clin Med, Zhengzhou, Peoples R China
2.Chinese Acad Sci, High Field Magnet Lab, Hefei Inst Phys Sci, Hefei, Peoples R China
3.Jinan Univ, Key Lab Regenerat Med, Minist Educ, Dept Dev & Regenerat Biol, Guangzhou, Peoples R China
4.Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China
5.Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, CAS Ctr Excellence Mol Cell Sci, Sch Life Sci, Hefei, Peoples R China
6.Univ Sci & Technol China, Affiliated Hosp 1, Hefei, Peoples R China
7.Zhengzhou Univ, Translat Res Inst, Henan Prov Peoples Hosp, Acad Med Sci, Zhengzhou, Peoples R China
8.Univ Newcastle, Sch Environm & Life Sci, Newcastle, NSW, Australia
9.Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW, Australia
推荐引用方式
GB/T 7714		 Sun, Xuedan,Thorne, Rick Francis,Zhang, Xu Dong,et al. LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1 alpha-FOXO4-p21-dependent signaling axis[J]. EMBO REPORTS,2020,21.
APA Sun, Xuedan.,Thorne, Rick Francis.,Zhang, Xu Dong.,He, Miao.,Li, Jinming.,...&Wu, Mian.(2020).LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1 alpha-FOXO4-p21-dependent signaling axis.EMBO REPORTS,21.
MLA Sun, Xuedan,et al."LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1 alpha-FOXO4-p21-dependent signaling axis".EMBO REPORTS 21(2020).

入库方式： OAI收割

来源：合肥物质科学研究院

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