Clinical Significance of Long Intergenic Noncoding RNA-p21 in Colorectal Cancer

被引:126
作者
Zhai, Haiyan [1 ]
Fesler, Andrew [1 ]
Schee, Kristina [2 ]
Fodstad, Oystein [2 ]
Flatmark, Kjersti [2 ,3 ]
Ju, Jingfang [1 ]
机构
[1] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA
[2] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Tumor Biol, Oslo, Norway
[3] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Surg Gastroenterol, Oslo, Norway
关键词
Colorectal cancer; lincRNA-p21; p53; BETA-CATENIN EXPRESSION; COLON-CANCER; DIFFERENTIAL EXPRESSION; PROGNOSTIC-SIGNIFICANCE; RNA HOTAIR; P53; CELLS; CHEMORESISTANCE; OSTEOSARCOMA; ACCUMULATION;
D O I
10.1016/j.clcc.2013.06.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The impact of long intergenic noncoding RNA (lincRNA)-p21 on colorectal cancer (CRC) progression was investigated in this study. Wild-type p53 induces endogenous lincRNA-p21 in HCT-116 colon cancer cells. Elevated levels of lincRNA-p21 were significantly associated with CRC disease state, pT, and vascular invasion, indicating that lincRNA-p21 may contribute to CRC progression. Background: Long intergenic noncoding RNAs (lincRNAs) have been shown to be novel regulators for both transcription and posttranscriptional/translation. One of them, lincRNA-p21, was regulated by p53 and contributed to apoptosis in mouse embryonic fibroblasts. However, the impact of such regulation on colorectal cancer (CRC) remains to be determined. Methods: Total RNA was extracted from CRC cell lines and snap fresh frozen CRC samples from 2 CRC patient cohorts. The expression of lincRNA-p21 was quantified by quantitative real-time polymerase chain reaction analysis. Results: We discovered that the expression level of lincRNA-p21 was increased by elevated wild-type p53 induced by nutlin-3 in HCT-116 colon cancer cells. The expression level of lincRNA-p21 was significantly (P = .0208) lower in CRC tumor tissue when compared with the paired normal tissue from the same patient. There was no significant correlation of lincRNA-p21 with p53 status (wild-type vs. mutant). Tumors in the rectum showed a higher level of lincRNA-p21 than tumors in the colon (P = .00005). In addition, lincRNA-p21 in patients with stage III tumors was significantly higher than in those with stage I tumors (P = .007). Elevated levels of lincRNA-p21 were significantly associated with higher pT (P = .037 between pT 2 and 3) and vascular invasion (P = .017). Conclusions: These results indicate that lincRNA-p21 may contribute to CRC disease progression.
引用
收藏
页码:261 / 266
页数:6
相关论文
共 35 条
[1]   Requirement for p53 and p21 to sustain G2 arrest after DNA damage [J].
Bunz, F ;
Dutriaux, A ;
Lengauer, C ;
Waldman, T ;
Zhou, S ;
Brown, JP ;
Sedivy, JM ;
Kinzler, KW ;
Vogelstein, B .
SCIENCE, 1998, 282 (5393) :1497-1501
[2]   OVEREXPRESSION OF C-JUN, JUNB, OR JUND AFFECTS CELL-GROWTH DIFFERENTLY [J].
CASTELLAZZI, M ;
SPYROU, G ;
LAVISTA, N ;
DANGY, JP ;
PIU, F ;
YANIV, M ;
BRUN, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (20) :8890-8894
[3]  
Crawford L V, 1984, Mol Biol Med, V2, P261
[4]  
DONG ZG, 1995, INT J ONCOL, V7, P359
[5]   Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma [J].
Elzagheid, Adam ;
Buhmeida, Abdelbaset ;
Korkeila, Eija ;
Collan, Yrjo ;
Syrjanen, Kari ;
Pyrhonen, Seppo .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (24) :3866-3871
[6]   The expression of p53 and bcl-2 in gastrointestinal stromal tumours is associated with anatomical site, and p53 expression is associated with grade and clinical outcome [J].
Feakins, RM .
HISTOPATHOLOGY, 2005, 46 (03) :270-279
[7]   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
[8]   The hallmarks of cancer A long non-coding RNA point of view [J].
Gutschner, Tony ;
Diederichs, Sven .
RNA BIOLOGY, 2012, 9 (06) :703-719
[9]   A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response [J].
Huarte, Maite ;
Guttman, Mitchell ;
Feldser, David ;
Garber, Manuel ;
Koziol, Magdalena J. ;
Kenzelmann-Broz, Daniela ;
Khalil, Ahmad M. ;
Zuk, Or ;
Amit, Ido ;
Rabani, Michal ;
Attardi, Laura D. ;
Regev, Aviv ;
Lander, Eric S. ;
Jacks, Tyler ;
Rinn, John L. .
CELL, 2010, 142 (03) :409-419
[10]   Prognostic Significance of miR-215 in Colon Cancer [J].
Karaayvaz, Mihriban ;
Pal, Timothy ;
Song, Bo ;
Zhang, Cecilia ;
Georgakopoulos, Penelope ;
Mehmood, Saira ;
Burke, Stephanie ;
Shroyer, Kenneth ;
Ju, Jingfang .
CLINICAL COLORECTAL CANCER, 2011, 10 (04) :340-347