Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression
Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression
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外泌体介导的长非编码RNA ZFAS1转移促进胃癌进展
DOI：
10.1007/s00432-017-2361-2
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发表时间：
2017-06-01
影响因子：
3.6
通讯作者：
Zhang, Xu
中科院分区：
文献类型：
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作者：
Pan, Lei;Liang, Wei;Zhang, Xu
背景ZFAS1是一种新发现的长链非编码RNA（lncRNA），可促进肿瘤生长和转移。外泌体通过传递活性分子来介导癌症中的细胞通讯。 ZFAS1 在循环外泌体中的存在以及外泌体 ZFAS1 在胃癌 (GC) 中的作用仍然未知。本研究的目的是探讨外泌体ZFAS1在GC中的潜在作用。方法采用qRT-PCR检测肿瘤组织、血清样本、GC患者血清外泌体和细胞系中ZFAS1的表达。分析ZFAS1表达与临床病理特征的相关性。使用透射电子显微镜（TEM）、纳米颗粒跟踪分析（NTA）和蛋白质印迹来鉴定外泌体的特征。使用细胞计数、细胞集落形成和 Transwell 迁移测定研究 ZFAS1 在 GC 细胞生长和迁移中的生物学作用。利用流式细胞术、蛋白质印迹和qRT-PCR证明了ZFAS1的潜在机制。结果ZFAS1在GC细胞、肿瘤组织、GC患者血清和血清外泌体中表达升高。 ZFAS1表达增加与淋巴结转移和TNM分期显着相关。 ZFAS1敲低通过抑制细胞周期进程、诱导细胞凋亡和抑制上皮间质转化（EMT）来抑制GC细胞的增殖和迁移。相反，ZFAS1过表达促进GC细胞的增殖和迁移。此外，ZFAS1存在于外泌体中，并且可以通过外泌体传递来增强GC细胞的增殖和迁移。结论ZFAS1可以通过外泌体传递来促进GC进展，这表明ZFAS1可以作为GC潜在的诊断和预后生物标志物。
BackgroundZFAS1 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.MethodsThe 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.ResultsZFAS1 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.ConclusionZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.