气候变化领域集成服务门户(CCPortal): Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer

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DOI	10.1073/pnas.2025647118
	Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer
	Miyata K.; Imai Y.; Hori S.; Nishio M.; Loo T.M.; Okada R.; Yang L.; Nakadai T.; Maruyama R.; Fujii R.; Ueda K.; Jiang L.; Zheng H.; Toyokuni S.; Sakata T.; Shirahige K.; Kojima R.; Nakayama M.; Oshima M.; Nagayama S.; Seimiya H.; Hirota T.; Saya H.; Hara E.; Takahashi A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:35
英文摘要	Cellular senescence causes a dramatic alteration of chromatin organization and changes the gene expression profile of proinflammatory factors, thereby contributing to various age-related pathologies through the senescence-associated secretory phenotype (SASP). Chromatin organization and global gene expression are maintained by the CCCTC-binding factor (CTCF); however, the molecular mechanism underlying CTCF regulation and its association with SASP gene expression remains unclear. We discovered that noncoding RNA (ncRNA) derived from normally silenced pericentromeric repetitive sequences directly impairs the DNA binding of CTCF. This CTCF disturbance increases the accessibility of chromatin and activates the transcription of SASP-like inflammatory genes, promoting malignant transformation. Notably, pericentromeric ncRNA was transferred into surrounding cells via small extracellular vesicles acting as a tumorigenic SASP factor. Because CTCF blocks the expression of pericentromeric ncRNA in young cells, the down-regulation of CTCF during cellular senescence triggers the up-regulation of this ncRNA and SASP-related inflammatory gene expression. In this study, we show that pericentromeric ncRNA provokes chromosomal alteration by inhibiting CTCF, leading to a SASP-like inflammatory response in a cell-autonomous and non-cell-autonomous manner and thus may contribute to the risk of tumorigenesis during aging. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CTCF; Pericentromeric RNA; Senescence; Senescence-associated secretory phenotype; Small extracellular vesicles
语种	英语
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/238816
作者单位	Project for Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan; Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan; Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan; Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, 332-0012, Japan; Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan; Gastroenterological Center, Department of Gastroenterological Surgery, Cancer Institute Hospital...
推荐引用方式 GB/T 7714	Miyata K.,Imai Y.,Hori S.,et al. Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer[J],2021,118(35).
APA	Miyata K..,Imai Y..,Hori S..,Nishio M..,Loo T.M..,...&Takahashi A..(2021).Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer.Proceedings of the National Academy of Sciences of the United States of America,118(35).
MLA	Miyata K.,et al."Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer".Proceedings of the National Academy of Sciences of the United States of America 118.35(2021).