Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression

被引:367
作者
Pan, Lei [1 ,2 ,3 ]
Liang, Wei [1 ]
Fu, Min [1 ,2 ]
Huang, Zhen-hua [1 ,2 ]
Li, Xia [1 ]
Zhang, Wen [1 ]
Zhang, Peng [1 ]
Qian, Hui [1 ]
Jiang, Peng-cheng [1 ,2 ]
Xu, Wen-rong [1 ]
Zhang, Xu [1 ]
机构
[1] Jiangsu Univ, Sch Med, Jiangsu Key Lab Med Sci & Lab Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[2] Jiangsu Univ, Dept Gen Surg, Affiliated Peoples Hosp, 8 Dianli Rd, Zhenjiang 212002, Jiangsu, Peoples R China
[3] Zhenjiang Emergency Med Rescuing Ctr, 1-19 Dingmao Bridge Rd, Zhenjiang 212002, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
LncRNA; ZFAS1; Gastric cancer; Exosomes; Biomarker; EXTRACELLULAR VESICLES; POOR-PROGNOSIS; METASTASIS; EXPRESSION; CELLS; PROLIFERATION; PREDICTS; PATHWAY;
D O I
10.1007/s00432-017-2361-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC. The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR. The correlation between ZFAS1 expression and the clinicopathological characteristics was analyzed. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. The biological roles of ZFAS1 in GC cell growth and mobility were investigated using cell counting, cell colony formation, and transwell migration assay. The potential mechanism of ZFAS1 was demonstrated using flow cytometry, western blot, and qRT-PCR. ZFAS1 expression was elevated in GC cells, tumor tissues, serum and serum exosomes of GC patients. The increased ZFAS1 expression was significantly correlated with lymphatic metastasis and TNM stage. ZFAS1 knockdown inhibited the proliferation and migration of GC cells by suppressing cell cycle progression, inducing apoptosis, and inhibiting epithelial-mesenchymal transition (EMT). On the contrary, ZFAS1 overexpression promoted the proliferation and migration of GC cells. Moreover, ZFAS1 was present in exosomes and could be transmitted by exosomes to enhance GC cell proliferation and migration. ZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.
引用
收藏
页码:991 / 1004
页数:14
相关论文
共 32 条
[1]
[Anonymous], 2016, ONCOTARGET
[2]
[Anonymous], 2016, ONCOTARGET
[3]
[Anonymous], ONCOTARGET
[4]
SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer [J].
Askarian-Amiri, Marjan E. ;
Crawford, Joanna ;
French, Juliet D. ;
Smart, Chanel E. ;
Smith, Martin A. ;
Clark, Michael B. ;
Ru, Kelin ;
Mercer, Tim R. ;
Thompson, Ella R. ;
Lakhani, Sunil R. ;
Vargas, Ana C. ;
Campbell, Ian G. ;
Brown, Melissa A. ;
Dinger, Marcel E. ;
Mattick, John S. .
RNA, 2011, 17 (05) :878-891
[5]
Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[6]
Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma [J].
Chun, Hyung Wook ;
Hong, Ran .
ONCOLOGY LETTERS, 2016, 12 (03) :1753-1762
[7]
Circulating Long RNAs in Serum Extracellular Vesicles: Their Characterization and Potential Application as Biomarkers for Diagnosis of Colorectal Cancer [J].
Dong, Lei ;
Lin, Wanrun ;
Qi, Peng ;
Xu, Mi-die ;
Wu, Xiaoben ;
Ni, Shujuan ;
Huang, Dan ;
Weng, Wei-wei ;
Tan, Cong ;
Sheng, Weiqi ;
Zhou, Xiaoyan ;
Du, Xiang .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2016, 25 (07) :1158-1166
[8]
Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[9]
Exosomal IncRNA-p21 levels may help to distinguish prostate cancer from benign disease [J].
Isin, Mustafa ;
Uysaler, Ege ;
Ozgur, Emre ;
Koseoglu, Hikmet ;
Sanli, Oner ;
Yucel, Omer B. ;
Gezer, Ugur ;
Dalay, Nejat .
FRONTIERS IN GENETICS, 2015, 6
[10]
Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development [J].
Karlsson, Oskar ;
Rodosthenous, Rodosthenis S. ;
Jara, Calvin ;
Brennan, Kasey J. ;
Wright, Robert O. ;
Baccarelli, Andrea A. ;
Wright, Rosalind J. .
EPIGENETICS, 2016, 11 (10) :721-729