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

来源：

ONCOLOGY REPORTS | 2020年 / 44卷 / 05期

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

页码：1961 / 1970

页数：10