Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 143, Issue 6, Pages 991-1004Publisher
SPRINGER
DOI: 10.1007/s00432-017-2361-2
Keywords
LncRNA; ZFAS1; Gastric cancer; Exosomes; Biomarker
Categories
Funding
- National Natural Science Foundation of China [81572075, 81201660]
- Natural Science Foundation of the Jiangsu Province [BK20141303]
- Jiangsu Province for Outstanding Sci-tech Innovation Team in Colleges and Universities [SJK2013-10]
- Jiangsu Province's Major Project in Research and Development [BE2015667]
- Key Research and Development Project of Zhenjiang [SH2016044]
- Zhenjiang Science and Technology support program [FZ2014043]
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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.
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