Elevated Expression of RPA3 Is Involved in Gastric Cancer Tumorigenesis and Associated with Poor Patient Survival

被引:21
作者
Dai, Zhongming [1 ,2 ]
Wang, Shufang [1 ]
Zhang, Weiping [3 ]
Yang, Yunsheng [1 ]
机构
[1] Peoples Liberat Army Gen Hosp, Dept Digest Dis, Beijing 100853, Peoples R China
[2] Xinjiang Mil Reg Gen Hosp, Dept Digest Dis, Urumqi 830000, Xinjiang Provin, Peoples R China
[3] Suzhou BenQ Hosp, Dept Digest Dis, Suzhou 215000, Jiangsu, Peoples R China
关键词
RPA3; Gastric cancer; Tumor progression; Poor survival; Prognostic biomarker; REPLICATION PROTEIN-A; DNA-DAMAGE; IN-VITRO; MUTATION; BREAST;
D O I
10.1007/s10620-017-4696-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The replication protein A3 (RPA3) is a component of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism. However, the involvement of RPA3 in gastric cancer tumorigenesis has not yet been investigated. We stably knocked down RPA3 expression using short hairpin RNA in AGS cell line, and performed cell growth, colony formation and soft agar assays. Xenograft experiments were performed to examine tumor promoting properties of RPA3 in vivo. The qRT-PCR and immunohistochemistry were performed to evaluate RPA3 expression levels in 37 and 12 pairs of gastric cancer patient samples, respectively. Association between RPA3 expression and survival was evaluated in an independent cohort of 85 gastric cancer patients. Downregulation of RPA3 inhibited cell growth, clonogenicity and soft agar growth in AGS cells. Decreased expression of RPA3 significantly reduced tumor growth rate in AGS xenografts. In addition, RPA3 was upregulated in cancerous tissues compared with matched noncancerous adjacent tissues in gastric cancer patients. High expression of RPA3 was associated with poor patient survival. Upregulation of RPA3 is involved in gastric cancer tumorigenesis and is associated with poorer patient survival. RPA3 represents a new therapeutic target of gastric cancer and serves as a potential prognostic biomarker for patient survival in gastric cancer.
引用
收藏
页码:2369 / 2375
页数:7
相关论文
共 25 条
[1]   Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A [J].
Bochkareva, E ;
Kaustov, L ;
Ayed, A ;
Yi, GS ;
Lu, Y ;
Pineda-Lucena, A ;
Liao, JCC ;
Okorokov, AL ;
Milner, J ;
Arrowsmith, CH ;
Bochkarev, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15412-15417
[2]   BRCA1 modulates ionizing radiation induced nuclear focus formation by the replication protein A p34 subnit [J].
Choudhary, SK ;
Li, R .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2002, 84 (04) :666-674
[3]   CELLULAR FACTORS REQUIRED FOR MULTIPLE STAGES OF SV40 DNA-REPLICATION INVITRO [J].
FAIRMAN, MP ;
STILLMAN, B .
EMBO JOURNAL, 1988, 7 (04) :1211-1218
[4]   A dynamic model for replication protein A (RPA) function in DNA processing pathways [J].
Fanning, Ellen ;
Klimovich, Vitaly ;
Nager, Andrew R. .
NUCLEIC ACIDS RESEARCH, 2006, 34 (15) :4126-4137
[5]   Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians [J].
Flynn, Rachel Litman ;
Zou, Lee .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2010, 45 (04) :266-275
[6]   Replication protein A is an independent prognostic indicator with potential therapeutic implications in colon cancer [J].
Givalos, Nikolaos ;
Gakiopoulou, Hariklia ;
Skliri, Melina ;
Bousboukea, Katerina ;
Konstantinidou, Anastasia E. ;
Korkolopoulou, Penelope ;
Lelouda, Maria ;
Kouraklis, Gregory ;
Patsouris, Efstratios ;
Karatzas, Gabriel .
MODERN PATHOLOGY, 2007, 20 (02) :159-166
[7]   Patterns of somatic mutation in human cancer genomes [J].
Greenman, Christopher ;
Stephens, Philip ;
Smith, Raffaella ;
Dalgliesh, Gillian L. ;
Hunter, Christopher ;
Bignell, Graham ;
Davies, Helen ;
Teague, Jon ;
Butler, Adam ;
Edkins, Sarah ;
O'Meara, Sarah ;
Vastrik, Imre ;
Schmidt, Esther E. ;
Avis, Tim ;
Barthorpe, Syd ;
Bhamra, Gurpreet ;
Buck, Gemma ;
Choudhury, Bhudipa ;
Clements, Jody ;
Cole, Jennifer ;
Dicks, Ed ;
Forbes, Simon ;
Gray, Kris ;
Halliday, Kelly ;
Harrison, Rachel ;
Hills, Katy ;
Hinton, Jon ;
Jenkinson, Andy ;
Jones, David ;
Menzies, Andy ;
Mironenko, Tatiana ;
Perry, Janet ;
Raine, Keiran ;
Richardson, Dave ;
Shepherd, Rebecca ;
Small, Alexandra ;
Tofts, Calli ;
Varian, Jennifer ;
Webb, Tony ;
West, Sofie ;
Widaa, Sara ;
Yates, Andy ;
Cahill, Daniel P. ;
Louis, David N. ;
Goldstraw, Peter ;
Nicholson, Andrew G. ;
Brasseur, Francis ;
Looijenga, Leendert ;
Weber, Barbara L. ;
Chiew, Yoke-Eng .
NATURE, 2007, 446 (7132) :153-158
[8]   Replication protein A (RPA): The eukaryotic SSB [J].
Iftode, C ;
Daniely, Y ;
Borowiec, JA .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1999, 34 (03) :141-180
[9]  
Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI [10.3322/caac.20006, 10.3322/caac.21254, 10.3322/caac.21332, 10.3322/caac.21551, 10.3322/caac.20073, 10.3322/caac.21387, 10.3322/caac.21654, 10.3322/caac.21601]
[10]   Prognostic significance of replication protein A (RPA) expression levels in bladder urothelial carcinoma [J].
Levidou, Georgia ;
Gakiopoulou, Hariklia ;
Kavantzas, Nikolaos ;
Saetta, Angelica A. ;
Karlou, Maria ;
Pavlopoulos, Petros ;
Thymara, Irene ;
Diamantopoulou, Kalliopi ;
Patsouris, Efstratios ;
Korkolopoulou, Penelope .
BJU INTERNATIONAL, 2011, 108 (2B) :E59-E65