The Study Of Secreting-cricRNAs In The Diagnosis Of Gastric Cancer And Its Role In Mediating Angiogenesis

Background and objective: Gastric cancer?GC?is one of the most common gastrointestinal tumors in the world.The incidence of gastric cancer is also in the forefront of malignant tumors and has obvious regional differences in China.Due to the increase of life pressure,the change of diet habits,the infection of Helicobacter pylori and so on,the incidence of gastric cancer shows a young trend.However,due to the lack of effective early diagnosis,gastric cancer is found at the middle and late stage and the prognosis is very poor.Similar to most solid tumors,the growth of gastric cancer requires a large amount of nutrients,and angiogenesis plays an important role in the development of gastric cancer.At present,the antiangiogenic drugs for gastric cancer are mostly second and third line therapy,so the study of angiogenesis in gastric cancer still needs further exploration.In order to improve the early diagnosis of gastric cancer,non-invasive and more sensitive diagnostic methods are widely studied.Circ RNAs are indentified as a novel and stable non-coding RNAs.Exosomes are cell-derived small membrane vesicles,which mediate cell-cell communication by transporting various RNAs,including circ RNAs.Tumor microenvironment and its communication with tumor cells directly determine the malignancy of tumor.The occurrence,development,metastasis and drug resistance of tumor can not be separated from the role of matrix.Exosomes are a key component of extracellular matrix which plays a key role in cell-cell communication in recent years.Tumor delivery exosomes interacting with stromal cells in tumor microenvironment promotes metastasis and drug resistance of tumor cells.However,the role of exosomal circ RNAs in GC remains poorly defined.The purpose of this study is to explore the value of circular RNAs in the early diagnosis of gastric cancer and the effect of its adsorption function on angiogenesis,and to provide a new idea for early diagnosis and antiangiogenic therapy of gastric cancer.Methods: 1.Exosomes are isolated from the plasma of GC patients and healthy individuals,and total exosomal RNAs were extracted.RNA microarray technique was used to predict the profiling of exosomal circ RNAs in mixed plasma of 18 GC patients and 12 healthy individuals.And its expression level was confirmed with additional 50 GC patients and 19 healthy volunteers.We used the receiver operating characteristic curve?ROC?to verify the diagnostic accuracy.2.The morphology and expression of exocrine were confirmed by electron microscope and Western blot technique.The miR-29 a up-regulation / down-regulation of SGC7901 cells by miR-29 a ????mimics?/ ????inhibitors?and circular RNAs interference plasmid induced circ RNA?hsa_circ₀044366?down-regulation in SGC7901 cells.Then the exosomes were extracted from the cells to treat the HUVEC cells.3.We also investigated the functional role of circ RNAs in HUVEC cells by relevant experiments?the transwell,angiogenesis assays and Edu assays?.Results: 1.Four cirRNAs?hsa_circ₀082109,0072525,0065755 and 0010522?were found to be remarkably up-regulated in GC plasma.The area under the ROC curve?AUC?of these circ RNAs were 0.938,0.942,0.958 and 0.982;and their sensitivity and specificity were?0.84,0.95?,?0.98,0.95?,?0.8,0.95?,?0.92,0.79?,respectively.2.Functional experiments have demonstrated that cicr RNAs?hsa_circ₀044366?can promote the proliferation and migration of vascular cells by miR-29 a adsorption.Conclusions: Our study suggested that these exosomal circ RNAs were significantly up-regulated in GC plasma and may be as novel non-invasive biomarker for GC diagnosis.Similarly,cicr RNAs can play a role in angiogenesis by adsorbing sponges.