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.
Highlights
renal cell carcinoma (RCC) is the most common carcinoma of the adult kidney, accounting for the majority (90%) of kidney cancer cases
RUNX3 expression is decreased in human RCC We first determined whether RUNX3 expression is changed in human RCC
We used tissue microarray (TMA) technology, immunohistochemistry and Western blot to investigate the role of RUNX3 in RCC
Summary
RCC is the most common carcinoma of the adult kidney, accounting for the majority (90%) of kidney cancer cases. Its incidence has gradually increased during the last decades [1]. Surgical resection is the most effective treatment for localized RCC tumors. 30% of patients develop metastatic disease after surgery [2], and median survival of those patients is only about 13 months [3]. Novel diagnostic and therapeutic markers are urgently needed for this disease. Discovery of biomarkers and their application in conjunction with traditional cancer diagnosis, clinical staging, and prognosis would contribute to improving early diagnosis and patient therapy
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