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

文献类型：期刊论文

作者Yang, Rui5,6; Liu, Na5,6; Chen, Ling5,6; Jiang, Yiqun5,6,7; Shi, Ying5,6; Mao, Chao5,6; Liu, Yating5,6; Wang, Min5,6; Lai, Weiwei5,6; Tang, Haosheng5,6
刊名ONCOGENE
出版日期2019-11-14
卷号38期号:46页码:7133-7145
ISSN号0950-9232
DOI10.1038/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.
WOS关键词LONG NONCODING RNA ; LYMPHOID-SPECIFIC HELICASE ; GENE-EXPRESSION ; METHYLATION PATTERNS ; DNA METHYLATION ; BINDING-SITE ; GINS COMPLEX ; REPRESSION ; AXIS ; PHOSPHORYLATION
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
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.

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来源：上海药物研究所

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