Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA

doi:10.1074/jbc.M115.683813

科研成果详情

题名	Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA
作者	Yu, Fujun 1; Zheng, Jianjian2; Mao, Yuqing 1; Dong, Peihong3; Lu, Zhongqiu4; Li, Guojun 5; Guo, Chuanyong 6; Liu, Zhanju 6; Fan, Xiaoming 1,7
发表日期	2015-11-20
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	RNA interference (RNAi) competing endogenous RNA fibrosis growth arrest-specific transcript 5 hepatic stellate cell (HSC) liver fibrosis long non-coding RNA (long ncRNA, lncRNA) microRNA (miRNA) microRNA-222.
其他关键词	HEPATIC STELLATE CELLS ; TUMOR-SUPPRESSOR ; POOR-PROGNOSIS ; FEEDBACK LOOP ; CANCER ; PROLIFERATION ; EXPRESSION ; FIBROSIS ; MIRNAS ; ACTIVATION
摘要	Effective control of hepatic stellate cell (HSC) activation and proliferation is critical to the treatment of liver fibrosis, Long non-coding RNAs have been shown to play a pivotal role in the regulation of cellular processes. It has been reported that growth arrest-specific transcript 5 (GAS 5) acts as a crucial mediator in the control of cell proliferation and growth. However, little is known about the role and underlying mechanism of GAS5 in liver fibrosis. In this study, our results indicated that GAS5 expression was reduced in mouse, rat, and human fibrotic liver samples and in activated HSCs. Overexpression of GAS5 suppressed the activation of primary HSCs in vitro and alleviated the accumulation of collagen in fibrotic liver tissues in vivo. We identified GASS as a target of microRNA-222 (miR-222) and showed that miR-222 could inhibit the expression of GAS5. Interestingly, GAS5 could also repress miR-222 expression. A pulldown assay further validated that GAS5 could directly bind to miR-222. As a competing endogenous RNAs, GAS5 had no effect on primary miR-222 expression. In addition, GAS5 was mainly localized in the cytoplasm. Quantitative RT-PCR further demonstrated that the copy numbers of GAS5 per cell are higher than those of miR-222. GAS5 increased the level of p27 protein by functioning as a competing endogenous RNA for miR-222, thereby inhibiting the activation and proliferation of HSCs. Taken together, a new regulatory circuitry in liver fibrosis has been identified in which RNAs cross-talk by competing for shared microRNAs. Our findings may provide a new therapeutic strategy for liver fibrosis.
资助项目	Science and Technology Commission of Shanghai MunicipalityScience & Technology Commission of Shanghai Municipality (STCSM) [11ZR1405700]; Key Clinical Disciplines Construction of Shanghai Municipality [ZK2012B20]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000176/H0317, 81100292/H0317, 81500458/H0317]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [Y2090326, Y2110634, LY16H030012]; Wenzhou Municipal Science and Technology Bureau [Y20110033, Y20120127]; Wang Bao-En Liver Fibrosis Foundation [20120127]; Key Disciplines in Colleges and Universities of Zhejiang Province
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
出版地	BETHESDA
ISSN	1083-351X
EISSN	1083-351X
卷号	290 期号:47 页码:28286-28298
DOI	10.1074/jbc.M115.683813
页数	13
WOS类目	Biochemistry & Molecular Biology
WOS研究方向	Biochemistry & Molecular Biology
WOS记录号	WOS:000365761900021
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20154801604702
EI主题词	RNA
URL	查看原文
PubMed ID	26446789
PMC记录号	PMC4653684
SCOPUSEID	2-s2.0-84947776036
通讯作者地址	[Fan, Xiaoming]Department of Gastroenterology,Jinshan Hospital,Fudan University,1508 Longhang Rd.,Jinshan, Shanghai,201508,China
Scopus学科分类	Biochemistry;Molecular Biology;Cell Biology
TOP期刊	TOP期刊
引用统计	被引频次：107[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/8596
专题	附属第一医院
通讯作者	Fan, Xiaoming
作者单位	1.Department of Gastroenterology,Jinshan Hospital,Fudan University,1508 Longhang Rd.,Jinshan, Shanghai,201508,China; 2.Wenzhou Key Laboratory of Surgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Department of Infectious Diseases,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 4.Department of Emergency,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 5.Department of Hepatology,Ningbo Yinzhou Second Hospital,Ningbo,315000,China; 6.Department of Gastroenterology,Shanghai Tenth People's Hospital,Tongji University,School of Medicine,Shanghai,200072,China; 7.Department of Internal Medicine,Shanghai Medical College,Fudan University,Shanghai,201508,China
推荐引用方式 GB/T 7714	Yu, Fujun,Zheng, Jianjian,Mao, Yuqing,et al. Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(47):28286-28298.
APA	Yu, Fujun., Zheng, Jianjian., Mao, Yuqing., Dong, Peihong., Lu, Zhongqiu., ... & Fan, Xiaoming. (2015). Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA. JOURNAL OF BIOLOGICAL CHEMISTRY, 290(47), 28286-28298.
MLA	Yu, Fujun,et al."Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA".JOURNAL OF BIOLOGICAL CHEMISTRY 290.47(2015):28286-28298.