| Background Gastric cancer (GC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Despite efforts in diagnostic techniques and improvements in chemotherapy and radiotherapy, patients with advanced or metastatic gastric cancer still carry a poor prognosis and the median overall survival (OS) remains less than 1 year. One of the major cause of cancer associated mortality is tumor metastasis, thus, early diagnosis of GC is of particular significance for the prognosis.Long non-coding RNAs (lncRNAs) are a class of RNA molecules longer than 200 nucleotides with no or limited protein-coding potential. CircRNAs are a novel type of endogenous noncoding RNA, different from the linear RNAs, which form closed loop structures with a covalent bond linking the 3'and 5'ends. Recently, many studies have revealed that lncRNAs and circRNAs could play critical roles in many biological processes including cellular differentiation, invasion, and metastasis. Dysregulation of lncRNA and circRNA expression has been reported in different types of cancers. In addition, circulating noncoding RNAs has been applied for cancer diagnosis and prognosis, and also could be used as potential biomarkers and therapeutic targets for gastric cancer.Methords Here we selected 14 candidate cancer-related lncRNAs and several circRNAs from literature and a database that integrated published ncRNAs and their associated diseases. We examined the expression levels of the lncRNAs and circRNAs in cell lines, tissues and plasmas, and evaluated the correlations between ncRNA expression level in tumor tissues and plasmas and clinicopathological features to evaluate the potential diagnostic value. To investigate the relation of ZFAS1 and EMT markers, we divided the gastric cancer cells into two groups by biotinylated antibody and streptavidin coated magnetic particles to investigate the association between ZFAS1 and EMT markers. Finally, to confirm the association, we investigated the EMT markers in an EMT model induced by TGF-?1; Then we knockdown ZFAS1 by RNAi, and investigate the biological behavior after RNAi with wound healing, transwell migration assay and clone formation assay.Results In this study, the expression of fourteen cancer related lncRNAs were investigated in paired tissues of 66 patients with GC, realtime RT-PCR revealed that ZFAS1 was significantly up-regulated, and ZFAS1 was positively correlated with clinicopathological features of GC patients. We then examined the expression of ZFAS1 in plasmas derived from 77 GC patients before- and post-operations and 60 healthy individuals, and found that circulating ZFAS1 was also up-regulated in GC patients and operation can reduce its presence in plasma, also ZFAS1 was positively correlated with clinicopathological features of GC patients. To investigate the potential mechanisms, we compared the expression of ZFAS1 in multiple gastric cell lines and one normal cell line and found that ZFAS1 was up-regulated in GC cell lines. Furthermore, circulating tumor cells (CTC) were simulated by mixing GC cells with peripheral blood. After EpCAM antibody-based cell sorting, we found that the expression of ZFAS 1 was positively correlated with EMT property of CTCs. ZFAS1 and the mesenchymal markers ZEB1 and Snail were up-regulated after the cells were induced by TGF-?1. The down-regulation of ZFAS1 inhibited the clone formation, migration and invasion abilities of cancer cells. Taken together, our results suggested that ZFAS1 was up-regulated in both tissues and plasmas of GC patients, and may be involved in regulation of EMT in GC progression.CircRNA-Smarca5 was significantly down-regulated in tissues of gastric cancer. Circulating circRNA-Smarca5 was up-regulated in GC patients and operation can reduce its presence in plasma.Conclusions Our results showed that ZFAS1 may play an important role in gastric cancer invasion and metastasis through regulating EMT and may acts as a potential biomarker for diagnosis of gastric cancer; CircRNA-Smarca5 may act as a diagnostic and prognosis marker for gastric cancer. |
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