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As one of the most common malignant cancers in the world, gastric cancer is caused by mang factors among which tobacco smoke is an important risk factor. Gastric cancer stem cells (GCSCs) and the derived exosomes play a key role in the occurrence and development of gastric cancer, and exosomal circRNA is considered as a new regulatory factor in the development of gastric cancer. However, it is unclear whether tobacco smoke can affect exosomes and their transport circRNAs to promote the development of gastric cancer. Herein, we provided a new insight into tobacco smoke promoting the progression of gastric cancer. In the present study, we demonstrated that tobacco smoke-induced exosomes promoted the spheroidizing ability, stemness genes expression, and epithelial-mesenchymal transition (EMT) process of GCSCs. We further found that hsa-circRNA-000670 (circ670) was up-regulated in tissues of gastric cancer patients with smoking history, tobacco smoke-induced GCSCs, and their exosomes. Functional assays have shown that circ670 knockdown inhibited the stemness and EMT process of GCSCs, whereas circ670 overexpression appeared to have an opposite effect. Our findings indicated that exosomal circ670 promotes the development of tobacco smoke-induced gastric cancer, which may provide insight into the mechanism of tobacco smoke promoting the progression of gastric cancer.

Ling Lu,1,* Shikun Fang,2,* Yue Zhang,2 Longtao Jin,1 Wenrong Xu,2 Zhaofeng Liang2 1Child Healthcare Department, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212001, People’s Republic of China; 2Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaofeng LiangJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, People’s Republic of ChinaEmail liangzhaofeng@ujs.edu.cnAbstract: Gastric cancer (GC) is a common malignant tumor affecting human health, with occult onset and poor prognosis. Exosomes are extracellular vesicles secreted by almost all cells, which can reflect the state of source cells or tissues. It is reported that exosomes are involved in almost all processes of GC. Exosomes provided a window to understand changes in cell or tissue states by carrying active components such as circular RNAs (circRNAs). CircRNAs are a naturally occurring class of endogenous noncoding RNAs and abnormal expression during the occurrence and development of GC. Exosomal circRNAs are those circRNAs stably existing in exosomes and having high clinical values as novel potential diagnosis and prognosis biomarkers of GC, which have the characteristics of abnormal expression, tissue specificity and development stage specificity. Herein, we briefly summarize the functions and roles and the current research progress of exosomes and exosomal circRNAs in GC with a focus on the potential application for GC progression, diagnosis and prognosis. We also prospected the clinical application of exosomes and exosomal circRNAs in the future.Keywords: gastric cancer, exosomes, circRNAs, function

Circular RNAs (circRNAs) are newly discovered intriguing RNAs due to the covalently closed loop structure, high stability, tissue specificity, and functional diversity. In recent years, a large number of circRNAs have been identified through high-throughput sequencing technology and bioinformatics methods, the abnormal expression of circRNAs are closely related to many diseases including bladder cancer (BC). CircRNAs have been proven to have several functions, such as acting as a regulator of parental gene transcription, miRNA sponge and interacting with proteins to regulate its expression. In addition, some circRNAs have been identified to encode proteins. CircRNAs have the characteristics of high abundance, high stability, wide distribution in body fluids, tissue specificity, and developmental stage specificity, which determine that circRNAs has great potential to be utilized as biomarkers for BC. Herein, we briefly summarize the biogenesis, functions and roles, and the current research progress of circRNAs in BC with a focus on the potential application for BC diagnosis, treatment, and prognosis.