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

doi:10.15252/embr.201948796

	LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1 alpha-FOXO4-p21-dependent signaling axis
	Sun, Xuedan 8,9; Thorne, Rick Francis 1,2; Zhang, Xu Dong 1,3; He, Miao 4; Li, Jinming 1; Feng, Shanshan 5; Liu, Xiaoying 1,6; Wu, Mian 1,7,8,9
刊名	EMBO REPORTS
	2020-04-03
卷号	21
关键词	cellular senescence GUARDIN lncRNAs LRP130-PGC1 alpha p21
ISSN号	1469-221X
DOI	10.15252/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.
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关键词	LONG NONCODING RNA ; RAPAMYCIN ; MECHANISMS ; EXPRESSION ; LRPPRC ; CANCER ; CELLS ; P21(WAF1/CIP1) ; HOMEOSTASIS ; METABOLISM
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	WILEY
WOS记录号	WOS:000524354400004
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
内容类型	期刊论文
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.Zhengzhou Univ, Translat Res Inst, Henan Prov Peoples Hosp, Acad Med Sci, Zhengzhou, Peoples R China 2.Univ Newcastle, Sch Environm & Life Sci, Newcastle, NSW, Australia 3.Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW, Australia 4.Chinese Acad Sci, High Field Magnet Lab, Hefei Inst Phys Sci, Hefei, Peoples R China 5.Jinan Univ, Key Lab Regenerat Med, Minist Educ, Dept Dev & Regenerat Biol, Guangzhou, Peoples R China 6.Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China 7.Henan Univ, Key Lab Stem Cell Differentiat & Modificat, Sch Clin Med, Zhengzhou, Peoples R China 8.Univ Sci & Technol China, Affiliated Hosp 1, Hefei, Peoples R China 9.Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, CAS Ctr Excellence Mol Cell Sci, Sch Life Sci, Hefei, Peoples R China
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).