期刊
ARCHIVES OF MEDICAL RESEARCH
卷 50, 期 4, 页码 225-233出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.arcmed.2019.08.010
关键词
RCC; YAP; Angiogenesis; VEGFA; Gli2
资金
- National Natural Science Foundation of China, China (NSFC) [81602244]
- Natural Science Basic Research Plan in Shaanxi Province of China [2017JM8018]
Background. High vascularization is a major characteristic of renal cell carcinoma (RCC). Thus, exploration of molecules promoting the tumor vascularization in RCC is urgent. Yes-associated Protein (YAP) is an oncogene in many cancer types, and high YAP expression was correlated with worse overall survival of RCC patients according to The Cancer Genome Atlas (TCGA) database. However, whether YAP promotes tumor angiogenesis of RCC is still unknown. Methods. Western blotting assay, real-time Quantitive PCR analysis, and ELISA assay were used to detect the related gene expression. The function of YAP on tumor angiogenesis was investigated by HUVEC recruitment, tube formation, and rabbit cornea assay. The clinical relevance of several genes was analyzed in a public database. Results. knockdown of YAP decreased RCC cell-inducing HUVEC recruitment and tube formation. Moreover, tumor angiogenesis ability of 786-O cells was crippled by YAP knockdown in vivo. In addition, the expression of Vascular endothelial growth factors A (VEGFA) was positively correlated with YAP expression in RCC tumor tissues, and YAP promoted expression and secretion of VEGFA in RCC cells. Mechanistically, GLI family zinc finger 2 (Gli2) knockdown in RCC cells reduced both basic and YAP-induced VEGFA expression, HUVECs recruitment, and tube formation, indicating that Gli2 is necessary for YAP to promote expression of VEGFA. Conclusion. Taken together, our results demonstrate that YAP/Gli2 promotes VEGFA expression and tumor angiogenesis in RCC cells, which could provide novel therapeutic targets in RCC treatment. (C) 2019 IMSS. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据