Renal cell carcinoma (RCC) is one of the most common malignant cancers in the adult urinary system worldwide. Tumor angiogenesis is a critical process during cancer progression, as it modulates carcinogenesis and metastasis. In recent years, microRNA‑218 (miR‑218) has been confirmed to play a crucial role in tumor suppression. However, the role of miR‑218 in RCC angiogenesis remains unclear. In the present study, it was found that the expression of miR‑218 was decreased in RCC tumor tissues and cell lines as detected by real‑time PCR analysis. Tube formation assays and migration assays also confirmed that miR‑218 inhibited the interaction between RCC cells and vascular endothelial cells by suppressing proangiogenic factor vascular endothelial growth factor A (VEGFA) in RCC cells. miR‑218 also repressed the subcutaneous tumorigenesis of RCC cells in nude mice, and the corneal angiogenesis in rabbit eyes. The underlying molecular mechanism was elucidated; miR‑218 targets GRB2‑associated binding protein 2 (GAB2), thereby inhibiting the PI3K/AKT/mTOR/VEGFA pathway. These results provide new insights into the mechanism of RCC carcinogenesis and progression, suggesting that miRNA‑218 may be a therapeutic target for the treatment of RCC.
Keywords: renal cell carcinoma; microRNA 218; angiogenesis; GAB2; PI3K/AKT/mTOR.