Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
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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Acknowledgements
This work was supported by the National Natural Science Foundation of China (81572075, 81201660), the 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), the Key Research and Development Project of Zhenjiang (SH2016044), and the Zhenjiang Science and Technology support program (FZ2014043).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Jiangsu University. This article does not contain any studies with animals performed by any of the authors.
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Informed consent was obtained from all individual participants included in the study.
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L. Pan and W. Liang have contributed equally to this work.
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Pan, L., Liang, W., Fu, M. et al. Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression. J Cancer Res Clin Oncol 143, 991–1004 (2017). https://doi.org/10.1007/s00432-017-2361-2
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DOI: https://doi.org/10.1007/s00432-017-2361-2