Abstract
Emerging research indicates that circRNAs serve a crucial role in occurrence and development of cancers. This study aimed to uncover the biological role of hsa_circ_0000519 in the progression of LUAD (lung adenocarcinoma). hsa_circ_0000519 was identified by bioinformatic analysis, and its differential expression was validated in LUAD tissues and cell lines. CCK8, colony formation, wound healing, transwell assays, and xenograft tumor models were used to observe the biological functions of hsa_circ_0000519. FISH, RIP, dual luciferase reporter assays, and recovery experiments were implemented to explore the underlying mechanisms of hsa_circ_0000519. hsa_circ_0000519 was significantly upregulated in LUAD tissues and cell lines. The expression of hsa_circ_0000519 was positively correlated with T grade and TNM stage in patients with LUAD. Downregulation of hsa_circ_0000519 remarkably reduced cell proliferation, migration, invasion in vitro, and tumor growth in vivo. Mechanistic investigation demonstrated that hsa_circ_0000519 directly sponged hsa-miR-1296-5p to reduce its repressive impact on DARS as well as activate the PI3K/AKT/mTOR signaling pathway. The malignant phenotypes of LUAD cells induced by upregulation of hsa_circ_0000519 could be rescued by hsa-miR-1296-5p overexpression or knockdown of DARS. In conclusion, hsa_circ_0000519 promotes LUAD progression through the hsa-miR-1296-5p/DARS axis and may be expected as a novel biomarker and therapeutic for LUAD.