Background <p>Gastric cancer (GC) is one of the most prevalent and aggressive malignancies globally, characterized by high morbidity and mortality rates despite advancements in medical technologies and screening methods. Recent studies have suggested that long non-coding RNAs (lncRNAs), particularly aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1), may play significant roles in tumor progression; however, its specific function in GC remains unclear. Therefore, this study aimed to clarify the contribution of DARS-AS1 to the progression and prognosis of GC.</p> Methods <p>We utilized quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to assess DARS-AS1 and CD31 expression levels in GC tissues derived from various cohorts. Additionally, functional studies involving knockdown of DARS-AS1 in GC cells were conducted to evaluate the effects on migration and angiogenesis in human umbilical vein endothelial cells (HUVECs) mediated by exosomes.</p> Results <p>Our analyses revealed that DARS-AS1 is significantly upregulated in GC tissues and is associated with malignant progression and poor prognosis. Furthermore, elevated DARS-AS1 levels correlated positively with tumor microvessel density (MVD). The knockdown of DARS-AS1 resulted in decreased migration and tube-forming ability of HUVECs in vitro. Mechanistically, we demonstrated that the exosomal transfer of DARS-AS1 from GC cells activates the Wnt/β-catenin signaling pathway by targeting miR-605-5p, thus promoting angiogenesis.</p> Conclusion <p>Our findings highlight the pivotal role of DARS-AS1 in enhancing GC progression through the activation of angiogenesis via the Wnt signaling pathway. By elucidating the mechanism underlying DARS-AS1-mediated tumorigenesis, we posit that DARS-AS1 could serve as a prognostic biomarker and a potential therapeutic target for GC intervention, warranting further exploration in clinical settings.</p>