A novel lncRNA, LUADT1, promotes lung adenocarcinoma proliferation via the epigenetic suppression of p27

被引:111
作者
Qiu, M. [1 ,2 ]
Xu, Y. [1 ,3 ]
Wang, J. [1 ,4 ]
Zhang, E. [5 ]
Sun, M. [5 ]
Zheng, Y. [1 ,6 ]
Li, M. [1 ]
Xia, W. [1 ,2 ]
Feng, D. [1 ,2 ]
Yin, R. [1 ]
Xu, L. [1 ]
机构
[1] Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Key Lab Mol & Translat Canc Res, Dept Thorac Surg,Canc Inst Jiangsu Prov, Nanjing 210009, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Clin Coll 4, Nanjing 210000, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Clin Coll 1, Nanjing 210000, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Dept Sci Res, Affiliated Canc Hosp, Canc Inst Jiangsu Prov, Nanjing 210009, Peoples R China
[5] Nanjing Med Univ, Dept Biochem & Mol Biol, Nanjing 210000, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Affiliated Canc Hosp, Canc Inst Jiangsu Prov, Dept Nursing, Nanjing 210009, Peoples R China
关键词
LONG NONCODING RNA; CANCER SUSCEPTIBILITY; CELL-CYCLE; GENE; EXPRESSION; DIFFERENTIATION; LANDSCAPE; METASTASIS; REPRESSION; SMOKERS;
D O I
10.1038/cddis.2015.203
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of various cancers. However, few lncRNAs have been well characterized in lung adenocarcinoma (LUAD). Here, we identified the expression profile of lncRNAs and protein-coding genes via microarrays analysis of paired LUAD tissues and adjacent non-tumor tissues from five female non-smokes with LUAD. A total of 498 lncRNAs and 1691 protein-coding genes were differentially expressed between LUAD tissues and paired adjacent normal tissues. A novel lncRNA, LUAD transcript 1 (LUADT1), which is highly expressed in LUAD and correlates with T stage, was characterized. Both in vitro and in vivo data showed that LUADT1 knockdown significantly inhibited proliferation of LUAD cells and induced cell cycle arrest at the G0-G1 phase. Further analysis indicated that LUADT1 may regulate cell cycle progression by epigenetically inhibiting the expression of p27. RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that LUADT1 binds to SUZ12, a core component of polycomb repressive complex 2, and mediates the trimethylation of H3K27 at the promoter region of p27. The negative correlation between LUADT1 and p27 expression was confirmed in LUAD tissue samples. These data suggested that a set of lncRNAs and protein-coding genes were differentially expressed in LUAD. LUADT1 is an oncogenic lncRNA that regulates LUAD progression, suggesting that dysregulated lncRNAs may serve as key regulatory factors in LUAD progression.
引用
收藏
页码:e1858 / e1858
页数:11
相关论文
共 49 条
[1]   catRAPID omics: a web server for large-scale prediction of protein-RNA interactions [J].
Agostini, Federico ;
Zanzoni, Andreas ;
Klus, Petr ;
Marchese, Domenica ;
Cirillo, Davide ;
Gaetano Tartaglia, Gian .
BIOINFORMATICS, 2013, 29 (22) :2928-2930
[2]   Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A [J].
Arab, Khelifa ;
Park, Yoon Jung ;
Lindroth, Anders M. ;
Schaefer, Andrea ;
Oakes, Christopher ;
Weichenhan, Dieter ;
Lukanova, Annekatrin ;
Lundin, Eva ;
Risch, Angela ;
Meister, Michael ;
Dienemann, Hendrik ;
Dyckhoff, Gerhard ;
Herold-Mende, Christel ;
Grummt, Ingrid ;
Niehrs, Christof ;
Plass, Christoph .
MOLECULAR CELL, 2014, 55 (04) :604-614
[3]   Genetic diversity and relationship of Hedychium from Northeast India as dissected using PCA analysis and hierarchical clustering [J].
Basak, Supriyo ;
Ramesh, Aadi Moolam ;
Kesari, Vigya ;
Parida, Ajay ;
Mitra, Sudip ;
Rangan, Latha .
META GENE, 2014, 2 :459-468
[4]   EGFR Exon-Level Biomarkers of the Response to Bevacizumab/Erlotinib in Non-Small Cell Lung Cancer [J].
Baty, Florent ;
Rothschild, Sacha ;
Frueh, Martin ;
Betticher, Daniel ;
Droege, Cornelia ;
Cathomas, Richard ;
Rauch, Daniel ;
Gautschi, Oliver ;
Bubendorf, Lukas ;
Crowe, Susanne ;
Zappa, Francesco ;
Pless, Miklos ;
Brutsche, Martin .
PLOS ONE, 2013, 8 (09)
[5]   The 2004 World Health Organization classification of lung tumors [J].
Beasley, MB ;
Brambilla, E ;
Travis, WD .
SEMINARS IN ROENTGENOLOGY, 2005, 40 (02) :90-97
[6]   Noncoding RNA and Polycomb recruitment [J].
Brockdorff, Neil .
RNA, 2013, 19 (04) :429-442
[7]   Hierarchical clustering of gene expression patterns in the Eomes plus lineage of excitatory neurons during early neocortical development [J].
Cameron, David A. ;
Middleton, Frank A. ;
Chenn, Anjen ;
Olson, Eric C. .
BMC NEUROSCIENCE, 2012, 13
[8]   The role of EZH2 in tumour progression [J].
Chang, C-J ;
Hung, M-C .
BRITISH JOURNAL OF CANCER, 2012, 106 (02) :243-247
[9]   Lung cancer in never smokers - A review [J].
Couraud, Sebastien ;
Zalcman, Gerard ;
Milleron, Bernard ;
Morin, Franck ;
Souquet, Pierre-Jean .
EUROPEAN JOURNAL OF CANCER, 2012, 48 (09) :1299-1311
[10]   Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers [J].
Govindan, Ramaswamy ;
Ding, Li ;
Griffith, Malachi ;
Subramanian, Janakiraman ;
Dees, Nathan D. ;
Kanchi, Krishna L. ;
Maher, Christopher A. ;
Fulton, Robert ;
Fulton, Lucinda ;
Wallis, John ;
Chen, Ken ;
Walker, Jason ;
McDonald, Sandra ;
Bose, Ron ;
Ornitz, David ;
Xiong, Donghai ;
You, Ming ;
Dooling, David J. ;
Watson, Mark ;
Mardis, Elaine R. ;
Wilson, Richard K. .
CELL, 2012, 150 (06) :1121-1134