The circYTHDF2-miR-146a-5p-PRSS1 Axis Mediates the JAK2-STAT3 Pathway to Promote Gastric Cancer Progression

Background : Gastric cancer (GC) is a malignant tumor that poses a serious threat to human life and health.PRSS1 is a differentially expressed protein in gastric cancer identified by our research group in previous studies; however, the mechanism underlying its role in the initiation and progression of gastric cancer remains unclear. Recent studies have shown that circular RNAs (circRNAs) play an important role in the progression of a variety of cancers. Methods : Immunohistochemical staining and Enzyme-Linked Immunosorbent Assay (ELISA) were used to detect the expression of PRSS1 in gastric cancer tissues, and to investigate its biological functions. Through methods including bioinformatics analysis, RNA sequencing (RNA-seq), dual-luciferase reporter gene assay, RNA immunoprecipitation (RIP), and rescue experiment, the upstream regulatory mechanism of PRSS1 was investigated. Results : Taken together, we found that PRSS1 has potential diagnostic, prognostic, and therapeutic values in cancer. Herein, we demonstrate that the PRSS1 protein is highly expressed in gastric cancer tissues and sera, and that its expression in tissues is associated with the degree of gastric cancer differentiation. Furthermore, circYTHDF2 is upregulated and was shown to positively regulate the expression of PRSS1 by sponging miR-146a-5p. Fundamentally, PRSS1 affects the proliferation, invasion, and metastasis of GC cells by activating the JAK2/STAT3 pathway. Our findings suggest that the circYTHDF2/miR-146a-5p/PRSS1 axis is involved in the proliferation, invasion, and metastasis of gastric cancer via the JAK2/STAT3 signaling pathway, and may serve as a molecular target for the early diagnosis and prognosis of gastric cancer. Conclusion : Our findings suggest that the circYTHDF2/miR-146a-5p/PRSS1 axis is involved in the malignant biological behaviors of gastric cancer via the JAK2/STAT3 signaling pathway, and may serve as a molecular target for the early diagnosis and prognosis of gastric cancer.