title: RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma.
abstract: RUNX3 (runt-related transcription factor-3) is a known tumor suppressor gene which exhibits potent antitumor activity in several carcinomas. However, little is known about the role of RUNX3 in human renal cell carcinoma (RCC). To investigate the clinical relevance of RUNX3 in RCC patients, immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 75 RCC tissues and paired non-cancerous tissues by using tissue microarray (TMA). We also investigated the role of RUNX3 in RCC cell migration, invasion and angiogenesis. The RUNX3 expression was decreased dramatically in human RCC tissue. The RUNX3 expression was significantly correlated with tumor size (P<0.001), depth of invasion (P<0.001), and of TNM stage (P<0.001). Restoration of RUNX3 significantly decreased renal carcinoma cell migration and invasion capacity compared with controls. In addition, we found that overexpression of RUNX3 reduced the proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs). Gelatin zymography and Western blot showed that RUNX3 expression suppressed matrix metalloproteinase-9 (MMP-9) protein level and enzyme activity. Western blot and ELISA showed that RUNX3 restoration inhibited the expression and secretion of vascular endothelial growth factor (VEGF). Taken together, our studies indicate that decreased expression of RUNX3 in human RCC tissue is significantly correlated with RCC progression. Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC.
authors: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors: Feifei
authors: F
authors: Chen
authors: Jin
authors: J
authors: Bai
authors: Wang
authors: W
authors: Li
authors: Pengjin
authors: P
authors: Mei
authors: Hui
authors: H
authors: Liu
authors: Linlin
authors: L
authors: Li
authors: Zhenqiang
authors: Z
authors: Pan
authors: Yongping
authors: Y
authors: Wu
authors: Junnian
authors: J
authors: Zheng
mesh_terms: D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D050677:Core Binding Factor Alpha 3 Subunit / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9