GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH

doi:10.1038/s41388-019-0909-0

	GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH
	Yang, Rui 5,6; Liu, Na 5,6; Chen, Ling 5,6; Jiang, Yiqun 5,6,7; Shi, Ying 5,6; Mao, Chao 5,6; Liu, Yating 5,6; Wang, Min 5,6; Lai, Weiwei 5,6; Tang, Haosheng 5,6
刊名	ONCOGENE
	2019-11-14
卷号	38 期号:46 页码:7133-7145
ISSN号	0950-9232
DOI	10.1038/s41388-019-0909-0
通讯作者	Liu, Shuang(shuangliu2016@csu.edu.cn) ; Tao, Yongguang(taoyong@csu.edu.cn)
英文摘要	Elucidating mechanisms in tumor suppressors and epigenetic modifiers are needed to gain insights into the etiology and treatment of cancer, the interplay between long intergenic non-coding RNAs (lncRNAs) and chromatin remodeling remains unclear. Here, we showed that GIAT4RA, a poorly characterized lncRNA LOC102723729, was significantly decreased in lung cancer cells and tissues; while no association was observed with clinical risk factors, expression was linked with clinical stage and lymphatic metastasis. Higher expression of GIAT4RA was linked with overall survival in NSCLC. GIAT4RA inhibited many characteristics of tumorigenesis including cell growth, clonal formation, migration and invasion, epithelial-mesenchymal transition, tumor sphere and tumor growth in vivo. Mechanistically, GIAT4RA was essential for the degradation of chromatin modifier lymphoid-specific helicase (LSH) by counteracting the deubiquintination in proteasome pathway by binding to 227-589 AA of LSH. GIAT4RA interfered with ubiquitin hydrolase Uchl3-mediated interaction and stabilization of LSH. LSH knockdown rescued GIAT4RA-promoted features, and LSH overexpression prevented GIAT4RA-induced phenotypes. Taken together, lncRNA GIAT4RA plays a critical role in NSCLC adenocarcinoma as a ubiquitination regulator and tumor suppressor.
资助项目	National Natural Science Foundation of China[81672787] ; National Natural Science Foundation of China[81672991] ; National Natural Science Foundation of China[81874139] ; National Natural Science Foundation of China[81728014] ; National Natural Science Foundation of China[81672308] ; National Basic Research Program of China[2015CB553903] ; Fundamental Research Funds for the Central Universities[2017zzts828] ; Fundamental Research Funds for the Central Universities[2017zzts206]
WOS关键词	LONG NONCODING RNA ; LYMPHOID-SPECIFIC HELICASE ; GENE-EXPRESSION ; METHYLATION PATTERNS ; DNA METHYLATION ; BINDING-SITE ; GINS COMPLEX ; REPRESSION ; AXIS ; PHOSPHORYLATION
WOS研究方向	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000496930500002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281815]
专题	中国科学院上海药物研究所
通讯作者	Liu, Shuang; Tao, Yongguang
作者单位	1.Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Dept Oncol,Inst Med Sci, Changsha 410008, Hunan, Peoples R China 2.Cent S Univ, Xiangya Hosp 2, Dept Thorac Surg, Hunan Key Lab Tumor Models & Individualized Med, Changsha, Hunan, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zu Chongzhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 4.Yale Sch Med, Dept Pathol, New Haven, CT 06520 USA 5.Cent S Univ, Xiangya Hosp, Dept Pathol, Key Lab Carcinogenesis & Canc Invas,Minist Educ, Changsha 410078, Hunan, Peoples R China 6.Cent S Univ, Sch Basic Med, Canc Res Inst, Key Lab Carcinogenesis,Minist Hlth, Changsha 410078, Hunan, Peoples R China 7.Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha 410008, Hunan, Peoples R China
推荐引用方式 GB/T 7714	Yang, Rui,Liu, Na,Chen, Ling,et al. GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH[J]. ONCOGENE,2019,38(46):7133-7145.
APA	Yang, Rui.,Liu, Na.,Chen, Ling.,Jiang, Yiqun.,Shi, Ying.,...&Tao, Yongguang.(2019).GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH.ONCOGENE,38(46),7133-7145.
MLA	Yang, Rui,et al."GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH".ONCOGENE 38.46(2019):7133-7145.