Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells

doi:10.1186/s13046-021-02230-z

	Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells
	Li, Hongyan 1,2,3,4,5,6; Zhang, Hong 1,2,3,4,5,6; Huang, Guomin 1,3,4,5,6,7; Bing, Zhitong 5,6,8; Xu, Duling 1,3,4,5,6,7; Liu, Jiadi 1,3,4,5,6,7; Luo, Hongtao 9,10; An, Xiaoli 8
刊名	JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
	2022-01-24
卷号	41 期号:1 页码:20
关键词	Ribosomal protein S27a (RPS27a) Lung adenocarcinoma Apoptosis
DOI	10.1186/s13046-021-02230-z
通讯作者	Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要	Background: Depletion of certain ribosomal proteins induces p53 activation, which is mediated mainly by ribosomal protein L5 (RPL5) and/or ribosomal protein L11 (RPL11). Therefore, RPL5 and RPL11 may link RPs and p53 activation. Thus, this study aimed to explore whether RPs interact with RPL11 and regulate p53 activation in lung adenocarcinoma (LUAD) cells. Methods: The endogenous RPL11-binding proteins in A549 cells were pulled down through immunoprecipitation and identified with a proteomics approach. Docking analysis and GST-fusion protein assays were used to analyze the interaction of ribosomal protein S27a (RPS27a) and RPL11. Co-immunoprecipitation and in vitro ubiquitination assays were used to detect the effects of knockdown of RPS27a on the interaction between RPS27a and RPL11, and on p53 accumulation. Cell cycle, apoptosis, cell invasion and migration, cell viability and colony-formation assays were performed in the presence of knockdown of RPS27a. The RPS27a mRNA expression in LUAD was analyzed on the basis of the TCGA dataset, and RPS27a expression was detected through immunohistochemistry in LUAD samples. Finally, RPS27a and p53 expression was analyzed through immunohistochemistry in A549 cell xenografts with knockdown of RPS27a. Results: RPS27a was identified as a novel RPL11 binding protein. GST pull-down assays revealed that RPS27a directly bound RPL11. Knockdown of RPS27a weakened the interaction between RPS27a and RPL11, but enhanced the binding of RPL11 and murine double minute 2 (MDM2), thereby inhibiting the ubiquitination and degradation of p53 by MDM2. Knockdown of RPS27a stabilized p53 in an RPL11-dependent manner and induced cell viability inhibition, cell cycle arrest and apoptosis in a p53-dependent manner in A549 cells. The expression of RPS27a was upregulated in LUAD and correlated with LUAD progression and poorer prognosis. Overexpression of RPS27a correlated with upregulation of p53, MDM2 and RPL11 in LUAD clinical specimens. Knockdown of RPS27a increased p53 activation, thus, suppressing the formation of A549 cell xenografts in nude mice. Conclusions: RPS27a interacts with RPL11, and RPS27a knockdown enhanced the binding of RPL11 and MDM2, thereby inhibiting MDM2-mediated p53 ubiquitination and degradation; in addition, RPS27a as important roles in LUAD progression and prognosis, and may be a therapeutic target for patients with LUAD.
资助项目	National Key R&D Program of China[2018YFE0205100] ; National Natural Science Foundation of China[11875061] ; National Natural Science Foundation of China[11505244] ; National Natural Science Foundation of Gansu province[20JR5RA550] ; Key Program of the National Natural Science Foundation of China[U1632270] ; National Laboratory of Heavy ion Accelerator of Lanzhou[E0HIRFL03P]
WOS关键词	RIBOSOMAL-PROTEIN S27A ; PROMOTES PROLIFERATION ; P53 ; CANCER ; ACTIVATION ; DISRUPTION ; STRESS ; PERTURBATION ; IMPAIRMENT ; MECHANISM
WOS研究方向	Oncology
语种	英语
出版者	BMC
WOS记录号	WOS:000746611300001
资助机构	National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of Gansu province ; Key Program of the National Natural Science Foundation of China ; National Laboratory of Heavy ion Accelerator of Lanzhou
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/142310]
专题	中国科学院近代物理研究所
通讯作者	Zhang, Hong
作者单位	1.Chinese Acad Sci, Inst Modern Phys, Dept Med Phys, Lanzhou 730000, Peoples R China 2.Gansu Prov Isotope Lab, Lanzhou 730300, Peoples R China 3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China 4.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou 730000, Peoples R China 5.Univ Chinese Acad Sci, Sch Nucl Sci & Technol, Beijing 101408, Peoples R China 6.Adv Energy Sci & Technol Guangdong Lab, Huizhou 516029, Peoples R China 7.Univ Chinese Acad Sci, Beijing 100039, Peoples R China 8.Chinese Acad Sci, Inst Modern Phys, Dept Computat Phys, Lanzhou 730000, Peoples R China 9.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou 730000, Peoples R China 10.Radiat Oncol Gansu Prov Canc Hosp, Lanzhou 730030, Peoples R China
推荐引用方式 GB/T 7714	Li, Hongyan,Zhang, Hong,Huang, Guomin,et al. Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2022,41(1):20.
APA	Li, Hongyan.,Zhang, Hong.,Huang, Guomin.,Bing, Zhitong.,Xu, Duling.,...&An, Xiaoli.(2022).Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,41(1),20.
MLA	Li, Hongyan,et al."Loss of RPS27a expression regulates the cell cycle, apoptosis, and proliferation via the RPL11-MDM2-p53 pathway in lung adenocarcinoma cells".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 41.1(2022):20.