MicroRNA-218 inhibits tumor angiogenesis of human renal cell carcinoma by targeting GAB2

被引:14
作者
Mu, Lijun [1 ]
Guan, Bing [1 ]
Tian, Juanhua [1 ]
Li, Xiang [1 ]
Long, Qingzhi [1 ]
Wang, Meiyu [2 ]
Wang, Wen [3 ]
She, Junjun [4 ]
Li, Xudong [1 ]
Wu, Dapeng [1 ]
Du, Yuefeng [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Urol, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Imaging, Xian 710061, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Outpatient, Xian 710061, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gen Surg, Xian 710061, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
renal cell carcinoma; microRNA; 218; angiogenesis; GAB2; PI3K; AKT; mTOR; MTOR COMPONENT RICTOR; CANCER; EXPRESSION; PROGRESSION; MECHANISMS; SUPPRESSOR; PATHWAY; PROTEIN;
D O I
10.3892/or.2020.7759
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1961 / 1970
页数:10
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