Abstract
Gastric cancer is a major health burden worldwide. Circular RNAs (circRNAs) are a novel family of noncoding RNAs that are involved in multiple types of cancers, including gastric cancer. As biological functions and the underlying molecular mechanisms of the newly identified circRNA circ0007360 have not been investigated, our present study focused on the role of circ0007360 in the progression of gastric cancer. After characterizing circ0007360 as a cytoplasmic circRNA, we revealed the inhibitory effects of circ0007260 on the survival, migration, invasion, and stemness of gastric cancer cells. Subsequently, miR-762 was identified as a direct target microRNA (miRNA) of circ0007360 and was proved to act as a vital downstream transcript to fulfill the tumor-promoting effects in the absence of circ0007360. Furthermore, we demonstrated that interferon regulatory factor 7 (IRF7), which was validated as a target gene of miR-762, serves as an indirect target of circ0007360 to attenuate the progression of gastric cancer. Moreover, in vivo experiments confirmed the potentiation of gastric cancer cell growth and stemness upon depletion of circ0007360. In summary, our results revealed that activation of the circ0007360/miR-762/IRF7 axis is a novel mechanism for the attenuation of gastric cancer progression. Our study unveils the diagnostic and therapeutic values of circ0007360 in patients with gastric cancer.
Highlights
Gastric cancer, which has adenocarcinoma as a major subtype, is caused by multiple clinical factors
We demonstrated that interferon regulatory factor 7 (IRF7), which was validated as a target gene of miR-762, serves as an indirect target of circ0007360 to attenuate the progression of gastric cancer
Given the fact that circ0007360 is resistant to RNase R and is relatively stable in gastric cancer cells (Figures 1C,D), it is of great value to examine the expression pattern of circ0007360 in gastric cancer patient samples investigate whether circ0007360 can be utilized as a biomarker for gastric cancer diagnosis in the future
Summary
Gastric cancer, which has adenocarcinoma as a major subtype (accounting for 90% of all cases), is caused by multiple clinical factors. Helicobacter pylori infection is usually considered as an initial stimulus for the tumorigenesis of gastric cancer (Correa, 2013). Mutations in inflammatory response genes have been shown to strongly correlate with the initiation of gastric cancer by facilitating the colonization of bacteria (Persson et al, 2011). Polymorphisms in genes, such as inflammatory IL1B, are associated with the risk of gastric cancer (Camargo et al, 2006). The 5-year survival rate of patients with gastric cancer is less than 20% (Anderson et al, 2010). Developing effective biomarkers for diagnosis and prognosis is of great worth for patients with gastric cancer
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