MicroRNA–VEGF axis in gastric cancer: a novel therapeutic frontier

Gastric cancer (GC) remains a major global health burden, characterized by high mortality and frequent diagnosis at advanced stages. A key driver of its aggressive progression is angiogenesis, predominantly regulated by vascular endothelial growth factor (VEGF). In parallel, microRNAs (miRNAs)—small non-coding RNAs—have emerged as critical post-transcriptional regulators whose dysregulation profoundly contributes to tumor development and progression. This review highlights the intricate interplay between miRNAs and VEGF in GC, focusing on the molecular mechanisms by which specific miRNAs modulate VEGF expression and downstream signaling. Tumor-suppressive miRNAs, such as miR-29a, miR-126, and miR-4316, directly target VEGF-A to inhibit tumor growth and angiogenesis, whereas oncogenic miRNAs, including miR-210, enhance VEGF expression and pro-angiogenic phenotypes. Targeting this miRNA–VEGF axis represents a promising therapeutic strategy through the restoration of tumor-suppressive miRNAs or inhibition of oncogenic counterparts, potentially in synergy with existing treatments. However, clinical translation is challenged by issues related to in vivo delivery, stability, and specificity. Emerging technologies, including nanoparticle-based delivery systems and exosome-mediated transport, are beginning to overcome these obstacles. Integrating miRNA profiling into personalized treatment approaches may offer a new frontier in GC management, enabling targeted interventions to improve patient outcomes.