Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape

Abstract

Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of β-catenin into the nucleus by activating Wnt/β-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited theinfiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases.