Long Non-coding RNA GAS5 Functions as a Tumor Suppressor in Renal Cell Carcinoma

被引:229
作者
Qiao, Hui-Ping [1 ,2 ]
Gao, Wei-Shi [3 ]
Huo, Jian-Xin [2 ]
Yang, Zhan-Shan [1 ]
机构
[1] Soochow Univ, Coll Med, Sch Radiat Med & Protect, Suzhou, Jiangsu, Peoples R China
[2] Baotou Med Coll, Affiliated Hosp 1, Dept Radiooncol, Baotou, Peoples R China
[3] Inner Mongolia Autonomous Reg Hosp, Hohhot, Inner Mongolia, Peoples R China
基金
中国国家自然科学基金;
关键词
Renal cell carcinoma; Long non-coding RNAs; GAS5; EXPRESSING DIPHTHERIA-TOXIN; REGULATORY SEQUENCES; TARGETED THERAPY; RISING INCIDENCE; BREAST-CANCER; GROWTH-ARREST; GENE; PLASMID; H19; CHROMOSOME-1;
D O I
10.7314/APJCP.2013.14.2.1077
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.
引用
收藏
页码:1077 / 1082
页数:6
相关论文
共 35 条
[1]   Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences [J].
Amit, Doron ;
Hochberg, Abraham .
JOURNAL OF TRANSLATIONAL MEDICINE, 2010, 8
[2]   Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].
Birney, Ewan ;
Stamatoyannopoulos, John A. ;
Dutta, Anindya ;
Guigo, Roderic ;
Gingeras, Thomas R. ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Snyder, Michael ;
Dermitzakis, Emmanouil T. ;
Stamatoyannopoulos, John A. ;
Thurman, Robert E. ;
Kuehn, Michael S. ;
Taylor, Christopher M. ;
Neph, Shane ;
Koch, Christoph M. ;
Asthana, Saurabh ;
Malhotra, Ankit ;
Adzhubei, Ivan ;
Greenbaum, Jason A. ;
Andrews, Robert M. ;
Flicek, Paul ;
Boyle, Patrick J. ;
Cao, Hua ;
Carter, Nigel P. ;
Clelland, Gayle K. ;
Davis, Sean ;
Day, Nathan ;
Dhami, Pawandeep ;
Dillon, Shane C. ;
Dorschner, Michael O. ;
Fiegler, Heike ;
Giresi, Paul G. ;
Goldy, Jeff ;
Hawrylycz, Michael ;
Haydock, Andrew ;
Humbert, Richard ;
James, Keith D. ;
Johnson, Brett E. ;
Johnson, Ericka M. ;
Frum, Tristan T. ;
Rosenzweig, Elizabeth R. ;
Karnani, Neerja ;
Lee, Kirsten ;
Lefebvre, Gregory C. ;
Navas, Patrick A. ;
Neri, Fidencio ;
Parker, Stephen C. J. ;
Sabo, Peter J. ;
Sandstrom, Richard ;
Shafer, Anthony .
NATURE, 2007, 447 (7146) :799-816
[3]   Current Status of Targeted Therapy for Advanced Renal Cell Carcinoma [J].
Cho, In-Chang ;
Chung, Jinsoo .
KOREAN JOURNAL OF UROLOGY, 2012, 53 (04) :217-228
[4]   Rising incidence of renal cell cancer in the United States [J].
Chow, WH ;
Devesa, SS ;
Warren, JL ;
Fraumeni, JF .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 281 (17) :1628-1631
[5]   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
[6]   The hallmarks of cancer A long non-coding RNA point of view [J].
Gutschner, Tony ;
Diederichs, Sven .
RNA BIOLOGY, 2012, 9 (06) :703-719
[7]   Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth [J].
Hasenpusch, Guenther ;
Pfeifer, Corinna ;
Aneja, Manish Kumar ;
Wagner, Kai ;
Reinhardt, Dietrich ;
Gilon, Michal ;
Ohana, Patricia ;
Hochberg, Avraham ;
Rudolph, Carsten .
PLOS ONE, 2011, 6 (06)
[8]   Rising incidence of small renal masses: A need to reassess treatment effect [J].
Hollingsworth, John M. ;
Miller, David C. ;
Daignault, Stephanie ;
Hollenbeck, Brent K. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (18) :1331-1334
[9]   Large non-coding RNAs: missing links in cancer? [J].
Huarte, Maite ;
Rinn, John L. .
HUMAN MOLECULAR GENETICS, 2010, 19 :R152-R161
[10]  
Ito S, 2007, INT J ONCOL, V31, P261