Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2

被引:159
作者
Han, L. [1 ]
Zhang, E-b [2 ]
Yin, D-d [3 ]
Kong, R. [4 ]
Xu, T-p [1 ]
Chen, W-m [1 ]
Xia, R. [2 ]
Shu, Y-q [1 ]
De, W. [2 ]
机构
[1] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 1, Nanjing 210000, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Dept Biochem & Mol Biol, Nanjing 210029, Jiangsu, Peoples R China
[3] Southeast Univ, Affiliated Hosp 2, Canc Res & Therapy Ctr, Nanjing, Jiangsu, Peoples R China
[4] Subei Peoples Hosp, Lab Ctr, Yangzhou, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
UP-REGULATION; DIFFERENTIATION; PROLIFERATION; REPRESSION; PROMOTERS;
D O I
10.1038/cddis.2015.30
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is involved in diseases including cancer. Here, we investigated the the role of lncRNA PANDAR in the progression of non-small cell lung carcinoma (NSCLC). PANDAR, interacting with NF-YA, was generally downregulated in NSCLC tissues. In a cohort of 140 NSCLC patients, decreased PANDAR expression was negatively correlated with greater tumor size (P<0.001) and advanced TNM stage (P=0.002). Moreover, PANDAR could serve as an independent predictor for overall survival in NSCLC (P=0.015). Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. PANDAR overexpression significantly repressed the proliferation in vitro and in vivo. We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. To our knowledge, this is the first report which showed the role of PANDAR in the progression of NSCLC. The p53/PANDAR/NF-YA/Bcl-2 interaction might serve as targets for NSCLC diagnosis and therapy.
引用
收藏
页码:e1665 / e1665
页数:12
相关论文
共 27 条
[1]   Noncoding RNA in development [J].
Amaral, Paulo P. ;
Mattick, John S. .
MAMMALIAN GENOME, 2008, 19 (7-8) :454-492
[2]   A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes [J].
Carpenter, Susan ;
Aiello, Daniel ;
Atianand, Maninjay K. ;
Ricci, Emiliano P. ;
Gandhi, Pallavi ;
Hall, Lisa L. ;
Byron, Meg ;
Monks, Brian ;
Henry-Bezy, Meabh ;
Lawrence, Jeanne B. ;
O'Neill, Luke A. J. ;
Moore, Melissa J. ;
Caffrey, Daniel R. ;
Fitzgerald, Katherine A. .
SCIENCE, 2013, 341 (6147) :789-792
[3]   A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA [J].
Cesana, Marcella ;
Cacchiarelli, Davide ;
Legnini, Ivano ;
Santini, Tiziana ;
Sthandier, Olga ;
Chinappi, Mauro ;
Tramontano, Anna ;
Bozzoni, Irene .
CELL, 2011, 147 (02) :358-369
[4]   Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy [J].
Czabotar, Peter E. ;
Lessene, Guillaume ;
Strasser, Andreas ;
Adams, Jerry M. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (01) :49-63
[5]   Doxorubicin promotes transcriptional upregulation of Cdc25B in cancer cells by releasing Sp1 from the promoter [J].
Dalvai, M. ;
Mondesert, O. ;
Bugler, B. ;
Manenti, S. ;
Ducommun, B. ;
Dozier, C. .
ONCOGENE, 2013, 32 (42) :5123-5128
[6]   Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation [J].
Dinger, Marcel E. ;
Amaral, Paulo P. ;
Mercer, Tim R. ;
Pang, Ken C. ;
Bruce, Stephen J. ;
Gardiner, Brooke B. ;
Askarian-Amiri, Marjan E. ;
Ru, Kelin ;
Solda, Giulia ;
Simons, Cas ;
Sunkin, Susan M. ;
Crowe, Mark L. ;
Grimmond, Sean M. ;
Perkins, Andrew C. ;
Mattick, John S. .
GENOME RESEARCH, 2008, 18 (09) :1433-1445
[7]   NF-YA Underlies EZH2 Upregulation and Is Essential for Proliferation of Human Epithelial Ovarian Cancer Cells [J].
Garipov, Azat ;
Li, Hua ;
Bitler, Benjamin G. ;
Thapa, Roshan J. ;
Balachandran, Siddharth ;
Zhang, Rugang .
MOLECULAR CANCER RESEARCH, 2013, 11 (04) :360-369
[8]   A noncoding RNA is a potential marker of cell fate during mammary gland development [J].
Ginger, MR ;
Shore, AN ;
Contreras, A ;
Rijnkels, M ;
Miller, J ;
Gonzalez-Rimbau, MF ;
Rosen, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (15) :5781-5786
[9]   The IASLC lung cancer staging project: Proposals for the revision of he TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours [J].
Goldstraw, Peter ;
Crowley, John ;
Chansky, Kari ;
Giroux, Dorothy J. ;
Groome, Patti A. ;
Rami-Porta, Ramon ;
Postmus, Pieter E. ;
Rusch, Valerie ;
Sobin, Leslie .
JOURNAL OF THORACIC ONCOLOGY, 2007, 2 (08) :706-714
[10]   Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].
Gupta, Rajnish A. ;
Shah, Nilay ;
Wang, Kevin C. ;
Kim, Jeewon ;
Horlings, Hugo M. ;
Wong, David J. ;
Tsai, Miao-Chih ;
Hung, Tiffany ;
Argani, Pedram ;
Rinn, John L. ;
Wang, Yulei ;
Brzoska, Pius ;
Kong, Benjamin ;
Li, Rui ;
West, Robert B. ;
van de Vijver, Marc J. ;
Sukumar, Saraswati ;
Chang, Howard Y. .
NATURE, 2010, 464 (7291) :1071-U148