Circular RNA hsa_circ_0002669 is down-regulated by Helicobacter pylori and inhibits the gastric cancer progression via miR-223-3p/ARID1A axis

Circular RNAs (circRNAs) are a unique group of RNAs that lack both a 5'-cap and a 3'-polyadenylated tail structure. Current studies have revealed that dysregulated circRNA expression is intricately related to the onset and advancement of multiple malignancies. Here, the function and associated mechanism of hsa_circ_0002669 in gastric cancer (GC) was investigated. Results revealed a significant reduction of hsa_circ_0002669 in GC tissue samples, relative to adjacent normal tissues. Moreover, <i>Helicobacter pylori</i> infection was identified as a factor contributing to the decreased levels of hsa_circ_0002669 in GC. Functional experiments indicated that overexpression of hsa_circ_0002669 greatly suppressed GC cell growth, migration, and invasion, whereas its knockdown produced the opposite effects. Studies using subcutaneous tumor implantation and intravenous tail vein injection models in immunodeficient mice demonstrated that elevated hsa_circ_0002669 levels significantly attenuated tumor growth and lung metastasis. Mechanistic studies showed that hsa_circ_0002669 functions as a competing endogenous RNA (ceRNA), sequestering miR-223-3p, thus upregulating ARID1A, a key target of miR-223-3p. Furthermore, the tumor-promoting effects of hsa_circ_0002669 knockdown were partially counteracted by inhibiting miR-223-3p. These findings demonstrate the potential of hsa_circ_0002669 as a novel diagnostic marker and therapeutic target for GC.