RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma.

RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma.
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RUNX3 抑制人肾细胞癌的迁移、侵袭和血管生成。

DOI:
10.1371/journal.pone.0056241
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zheng J
Zheng J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen F;Bai J;Li W;Mei P;Liu H;Li L;Pan Z;Wu Y;Zheng J

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RUNX3(runt 相关转录因子 3)是一种已知的肿瘤抑制基因,在多种癌症中表现出有效的抗肿瘤活性。然而,人们对 RUNX3 在人肾细胞癌 (RCC) 中的作用知之甚少。为了研究 RUNX3 在 RCC 患者中的临床相关性,利用组织微阵列 (TMA) 进行免疫组织化学检测 RUNX3 在 75 个 RCC 组织和配对非癌组织中的临床相关性。我们还研究了 RUNX3 在 RCC 细胞迁移、侵袭和血管生成中的作用。人肾细胞癌组织中RUNX3的表达显着降低。 RUNX3表达与肿瘤大小(P<0.001)、浸润深度(P<0.001)和TNM分期(P<0.001)显着相关。与对照组相比,RUNX3的恢复显着降低了肾癌细胞的迁移和侵袭能力。此外,我们发现RUNX3的过度表达减少了人脐血管内皮细胞(HUVEC)的增殖和管形成。明胶酶谱和蛋白质印迹显示 RUNX3 表达抑制基质金属蛋白酶 9 (MMP-9) 蛋白水平和酶活性。 Western blot和ELISA显示RUNX3恢复抑制血管内皮生长因子(VEGF)的表达和分泌。综上所述,我们的研究表明,人类 RCC 组织中 RUNX3 表达的降低与 RCC 进展显着相关。 RUNX3表达的恢复显着抑制RCC细胞的迁移、侵袭和血管生成。这些发现为RUNX3在肾细胞癌迁移、侵袭和血管生成中的重要性提供了新的见解。
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.
DOI: 10.1002/cncr.25838
发表时间: 2011-06-15
期刊: CANCER
影响因子: 6.2
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通讯作者: Hsiao, Michael