Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer

被引:124
作者
Cui, Di [1 ]
Yu, Cai-Hua [2 ]
Liu, Min [3 ]
Xia, Qing-Qing [1 ]
Zhang, Yu-Feng [1 ]
Jiang, Wei-Long [1 ]
机构
[1] Nanjing Univ Chinese Med, Dept Respirat, Jiangyin Hosp Tradit Chinese Med, Jiangyin, Peoples R China
[2] Huzhou Cent Hosp, Dept Cardiothorac Surg, 198 Hongqi Rd, Huzhou 313003, Peoples R China
[3] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China
关键词
PVT1; Non-small cell lung cancer; Biomarker; Proliferation;
D O I
10.1007/s13277-015-4261-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Accumulating evidence has indicated that long non-coding RNA PVT1 is upregulated in various human cancers. However, it remains unclear whether PVT1 is involved in the development and progression of non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression, biological role, and clinical significance of PVT1 in NSCLC. Our results indicated that PVT1 expression was significantly increased in NSCLC tissues and cell lines, and its upregulation was associated with advanced T-stage and tumor-node-metastasis (TNM) stage and regional lymph node metastasis. PVT1 expression levels were robust in differentiating NSCLC tissues from controls. Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival and disease-free survival in NSCLC patients. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays indicated that knockdown of PVT1 remarkably inhibited NSCLC cell proliferation, whereas overexpression of PVT1 significantly promoted cellular proliferation. In addition, PVT1 knockdown increased the number of cells in the G0/G1 phase and reduced the number of cells in the S phase, while overexpression of PVT1 could promote cell cycle progression. Furthermore, our findings also revealed that the messenger RNA (mRNA) and protein expression of P15 and P21 was significantly upregulated in NSCLC cells transfected with PVT1 small interfering RNA (siRNA) and downregulated in cells transfected with pcDNA3.1-PVT1. In conclusion, our study demonstrated that PVT1 might serve as a promising biomarker for diagnosis and prognosis of NSCLC, and it could promote the proliferation of NSCLC cells by downregulating p15 and p21 expression.
引用
收藏
页码:4127 / 4134
页数:8
相关论文
共 14 条
[1]
Bunn Paul A Jr, 2004, Clin Lung Cancer, V6, P85
[2]
PVT1: A Rising Star among Oncogenic Long Noncoding RNAs [J].
Colombo, Teresa ;
Farina, Lorenzo ;
Macino, Giuseppe ;
Paci, Paola .
BIOMED RESEARCH INTERNATIONAL, 2015, 2015
[3]
Non-coding RNAs in human disease [J].
Esteller, Manel .
NATURE REVIEWS GENETICS, 2011, 12 (12) :861-874
[4]
The functional role of long non-coding RNA in human carcinomas [J].
Gibb, Ewan A. ;
Brown, Carolyn J. ;
Lam, Wan L. .
MOLECULAR CANCER, 2011, 10
[5]
Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer [J].
Guan, Yinghui ;
Kuo, Wen-Lin ;
Stilwell, Jackie L. ;
Takano, Hirokuni ;
Lapuk, Anna V. ;
Fridlyand, Jane ;
Mao, Jian-Hua ;
Yu, Mamie ;
Miller, Melinda A. ;
Santos, Jennifer L. ;
Kalloger, Steve E. ;
Carlson, Joseph W. ;
Ginzinger, David G. ;
Celniker, Susan E. ;
Mills, Gordon B. ;
Huntsman, David G. ;
Gray, Joe W. .
CLINICAL CANCER RESEARCH, 2007, 13 (19) :5745-5755
[6]
Cdks, cyclins and CKIs: roles beyond cell cycle regulation [J].
Lim, Shuhui ;
Kaldis, Philipp .
DEVELOPMENT, 2013, 140 (15) :3079-3093
[7]
Long non-coding RNAs: insights into functions [J].
Mercer, Tim R. ;
Dinger, Marcel E. ;
Mattick, John S. .
NATURE REVIEWS GENETICS, 2009, 10 (03) :155-159
[8]
Long Noncoding RNA MALAT-1 is a New Potential Therapeutic Target for Castration Resistant Prostate Cancer [J].
Ren, Shancheng ;
Liu, Yawei ;
Xu, Weidong ;
Sun, Yi ;
Lu, Ji ;
Wang, Fubo ;
Wei, Min ;
Shen, Jian ;
Hou, Jianguo ;
Gao, Xu ;
Xu, Chuanliang ;
Huang, Jiaoti ;
Zhao, Yi ;
Sun, Yinghao .
JOURNAL OF UROLOGY, 2013, 190 (06) :2278-2287
[9]
INHIBITORS OF MAMMALIAN G(1) CYCLIN-DEPENDENT KINASES [J].
SHERR, CJ ;
ROBERTS, JM .
GENES & DEVELOPMENT, 1995, 9 (10) :1149-1163
[10]
Cancer Statistics, 2014 [J].
Siegel, Rebecca ;
Ma, Jiemin ;
Zou, Zhaohui ;
Jemal, Ahmedin .
CA-A CANCER JOURNAL FOR CLINICIANS, 2014, 64 (01) :9-29