Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR-665/LASP1 and activating PI3K/AKT pathway

Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR-665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine, clone formation assay, Transwell invasion assay, wound-healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR-665 sponges and facilitate GC growth and metastasis via modulating miR-665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3-kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR-665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.