RUNX3 Suppresses Migration, Invasion and Angiogenesis of Human Renal Cell Carcinoma

Chen, Feifei; Bai, Jin; Li, Wang; Mei, Pengjin; Liu, Hui; Li, Linlin; Pan, Zhenqiang; Wu, Yongping; Zheng, Junnian
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Integrative Genome-Wide Gene Expression Profiling of Clear Cell Renal Cell Carcinoma in Czech Republic and in the United States. Wozniak, Magdalena B.; Le Calvez-Kelm, Florence; Abedi-Ardekani, Behnoush; Byrnes, Graham; Durand, Geoffroy; Carreira, Christine; Michelon, Jocelyne; Janout, Vladimir; Holcatova, Ivana; Foretova, Lenka; Brisuda, Antonin; Lesueur, Fabienne; McKay, James; Brennan, Paul; Scelo, Ghislaine // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted...

  • Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma. Patard, J.-J.; Rioux-Leclercq, N.; Masson, D.; Zerrouki, S.; Jouan, F.; Collet, N.; Dubourg, C.; Lobel, B.; Denis, M.; Fergelot, P. // British Journal of Cancer;10/20/2009, Vol. 101 Issue 8, p1417 

    Background: The von Hippel-Lindau gene (VHL) alteration, a common event in sporadic clear-cell renal-cell carcinoma (CCRCC), leads to highly vascularised tumours. Vascular endothelial growth factor (VEGF) is the major factor involved in angiogenesis, but the prognostic significance...

  • Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma. Morris, M. R.; Gentle, D.; Abdulrahman, M.; Clarke, N.; Brown, M.; Kishida, T.; Yao, M.; Teh, B. T.; Latif, F.; Maher, E. R. // British Journal of Cancer;1/29/2008, Vol. 98 Issue 2, p496 

    Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four...

  • Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in renal cell carcinoma. KERONG WU; LI ZHANG; YIWEI LIN; KAI YANG; YUE CHENG // Oncology Letters;2014, Vol. 8 Issue 1, p55 

    The present study was performed to explore the effects of Notch pathway inhibition on the proliferation and apoptosis of renal carcinoma cells. The expression levels of Notch1 and Jagged1 were examined by western blot analysis and immunohistochemistry in pathologically identified clear cell...

  • Collecting duct carcinoma of the kidney: an immunohistochemical study of 11 cases. Vecchione, Andrea; Galetti, Tommaso Prayer; Gardiman, Marina; Ishii, Hideshi; Giarnieri, Enrico; Pagano, Francesco; Gomella, Leonard G.; Croce, Carlo M.; Baffa, Raffaele // BMC Urology;2004, Vol. 4, p11 

    Background: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes...

  • Claudin-7 Immunohistochemistry in Renal Tumors. Hornsby, Christopher D.; Cohen, Cynthia; Amin, Mahul B.; Picken, Maria M.; Lawson, Diane; Qiqin Yin-Goen; Young, Andrew N. // Archives of Pathology & Laboratory Medicine;Oct2007, Vol. 131 Issue 10, p1541 

    Context.—The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas...

  • Decreased expression of Dkkl and Dkk3 in human clear cell renal cell carcinoma. CHANG-CHENG GUO; XIAO-LONG ZHANG; BIN YANG; JIANG GENG; BO PENG; JUN-HUA ZHENG // Molecular Medicine Reports;2014, Vol. 9 Issue 6, p2367 

    The expression patterns of the Dickkopf (Dkk) family of proteins varies in different cancers. In the present study, the expression levels of Dkkl and Dkk3 were investigated in clear cell renal cell carcinoma (ccRCC) tissues. Dkkl and Dkk3 serum levels were also examined in patients with ccRCC,...

  • Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression. Jae Yoon Choi; Hyun Ho Han; Young Tae Kim; Joo Hyun Lee; Baek Gil Kim; Suki Kang; Nam Hoon Cho // Yonsei Medical Journal;Jan2017, Vol. 58 Issue 1, p59 

    Purpose: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative ovarian cancer that is intermediary between serous and endometrioid subtypes, in regards to molecular and clinical behaviors. However,...

  • Clinical Significance of SASH1 Expression in Glioma. Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei // Disease Markers;9/6/2015, p1 

    Objective. SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. Methods. We...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics