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:152
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
来源
CELL DEATH & DISEASE | 2015年 / 6卷
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
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