气候变化领域集成服务门户(CCPortal): Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP

CCPortal

DOI	10.1073/pnas.2026813118
	Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP
	Chen Y.; Hao Q.; Wang S.; Cao M.; Huang Y.; Weng X.; Wang J.; Zhang Z.; He X.; Lu H.; Zhou X.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:29
英文摘要	p53 inactivation is highly associated with tumorigenesis and drug resistance. Here, we identify a long noncoding RNA, the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP), as an inhibitor of p53. RMRP is overexpressed and associated with an unfavorable prognosis in colorectal cancer. Ectopic RMRP suppresses p53 activity by promoting MDM2-induced p53 ubiquitination and degradation, while depletion of RMRP activates the p53 pathway. RMRP also promotes colorectal cancer growth and proliferation in a p53-dependent fashion in vitro and in vivo. This anti-p53 action of RMRP is executed through an identified partner protein, SNRPA1. RMRP can interact with SNRPA1 and sequester it in the nucleus, consequently blocking its lysosomal proteolysis via chaperone-mediated autophagy. The nuclear SNRPA1 then interacts with p53 and enhances MDM2-induced proteasomal degradation of p53. Remarkably, ablation of SNRPA1 completely abrogates RMRP regulation of p53 and tumor cell growth, indicating that SNRPA1 is indispensable for the anti-p53 function of RMRP. Interestingly and significantly, poly (ADP-ribose) polymerase (PARP) inhibitors induce RMRP expression through the transcription factor C/EBPβ, and RMRP confers tumor resistance to PARP inhibition by preventing p53 activation. Altogether, our study demonstrates that RMRP plays an oncogenic role by inactivating p53 via SNRPA1 in colorectal cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	P53 \| long noncoding RNA \| RMRP \| SNRPA1 \| PARP inhibition
语种	英语
scopus关键词	CCAAT enhancer binding protein beta; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; protein p53; ribonuclease; RNA binding protein; RNA processing endoribonuclease; small nuclear ribonucleoprotein; unclassified drug; untranslated RNA; long untranslated RNA; mouse double minute 2 homolog; protein binding; protein p53; RMRP non-coding RNA, human; small nuclear ribonucleoprotein; TP53 protein, human; U2A' protein, human; animal cell; animal experiment; animal model; animal tissue; Article; cancer cell culture; cancer growth; cancer inhibition; cancer prognosis; cancer tissue; carcinogenesis; cell cycle progression; cell proliferation; cell viability; cell viability assay; chaperone-mediated autophagy; chromatin immunoprecipitation; colony formation; colorectal cancer; colorectal cancer cell line; CRISPR-CAS9 system; enzyme activity; gene editing; gene expression; gene knockdown; gene overexpression; immunoprecipitation; in situ hybridization; luciferase assay; male; mass spectrometry; mouse; mRNA expression level; nonhuman; overall survival; protein degradation; protein expression; protein interaction; pull-down assay; real time polymerase chain reaction; RNA extraction; RNA immunoprecipitation; RNA processing; RNA sequencing; tumor growth; tumor resistance; tumor volume; tumor xenograft; ubiquitination; colorectal tumor; down regulation; gene expression regulation; genetics; human; metabolism; tumor cell line; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Protein Binding; Proto-Oncogene Proteins c-mdm2; Ribonucleoprotein, U2 Small Nuclear; RNA, Long Noncoding; Tumor Suppressor Protein p53
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251120
作者单位	Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China; Department of Biochemistry & Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, United States; Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, United States; Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
推荐引用方式 GB/T 7714	Chen Y.,Hao Q.,Wang S.,et al. Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP[J],2021,118(29).
APA	Chen Y..,Hao Q..,Wang S..,Cao M..,Huang Y..,...&Zhou X..(2021).Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP.Proceedings of the National Academy of Sciences of the United States of America,118(29).
MLA	Chen Y.,et al."Inactivation of the tumor suppressor p53 by long noncoding RNA RMRP".Proceedings of the National Academy of Sciences of the United States of America 118.29(2021).