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.
Our data indicated that BRG1 expression is significantly increased in human glioma and it may be involved in the process of glioma cell proliferation, migration and invasion.
BackgroundThe pro-oncogenic anterior gradient 2 (AGR2) is involved in tumor growth and drug resistance of breast cancer. Mechanisms that regulate expression of AGR2 still need to be elucidated.MethodsIn this study, expression levels of AGR2 and miR-135b-5p were analyzed in different breast cancer cell lines as well as in clinical breast cancer tissues. The in vitro and in vivo functional effect of AGR2 and miR-135b-5p were also investigated. A luciferase reporter assay was applied to confirm the interaction between miR-135b-5p and AGR2 mRNA.ResultsWe identified AGR2 as a target of miR-135b-5p. Expression of AGR2 was up-regulated in doxorubicin-resistant breast cancer cells. AGR2 mediated doxorubicin-sensitivity of breast cancer cells both in vitro and in vivo. miR-135b-5p negatively regulated AGR2-expression of breast cancer cells increasing doxorubicin-sensitivity. However, miR-135b-5p was down-regulated in doxorubicin-resistant breast cancer cells as well as during treatment with doxorubicin, which might be a probable reason for over-expression of AGR2. Up-regulation of miR-135b-5p increased doxorubicin-sensitivity of breast cancer cells in vivo. In addition, levels of AGR2 negatively correlated with levels of miR-135b-5p in clinical breast cancer tissue samples.ConclusionOur results highlight the potential of miR-135b-5p as a target for treating AGR2-expressing breast cancer with doxorubicin-resistance.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1024-3) contains supplementary material, which is available to authorized users.
Our data indicated that RUNX3 expression is significantly decreased in human glioma, and targeting of the RUNX3 pathway may constitute a potential treatment modality for glioma.
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