Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma
ABSTRACT This study aimed to investigate the expression of ZEB1 in osteosarcoma tissues and to discuss the relationship between ZEB1 expression and osteosarcoma metastasis.
Using RT-PCR and Western blotting, the mRNA and protein expressions of ZEB1 in the osteosarcoma and normal bone tissues were detected. Using the RNA interference technique, the expression of ZEB1 in the human osteosarcoma MG-63 cell line was downregulated, and the changes in the invasion of MG-63 cells were examined.
The positive mRNA expression rate of ZEB1 in the osteosarcoma tissues was significantly higher than that in normal bone tissue (P < 0.05). The protein expression level of ZEB1 in the sarcoma tissues from patients with positive lung metastasis was significantly higher than that from patients without lung metastasis (P < 0.05). After the transfection of ZEB1 siRNA into the MG-63 cells, the protein expression of ZEB1 was significantly reduced (P < 0.05), and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (P < 0.05).
The overexpression of ZEB1 in osteosarcoma may be related to the carcinogenesis and development as well as metastasis and invasion of osteosarcoma.
- SourceAvailable from: Giovanni Battista Di Pierro[Show abstract] [Hide abstract]
ABSTRACT: Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using "bladder cancer" as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.Current Genomics 08/2012; 13(5):395-415. DOI:10.2174/138920212801619232 · 2.87 Impact Factor
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ABSTRACT: TRAF6, a unique tumor necrosis factor receptor-associated factor (TRAF) family member, possesses a unique receptor-binding specificity that results in its crucial role as the signaling mediator for TNF receptor superfamily and interleukin-1 receptor/Toll-like receptor superfamily. TRAF6 plays an important role in tumorigenesis, invasion and metastasis. This study aimed to explore the expression of TRAF6 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the relationship between TRAF6 expression and osteosarcoma invasion. These data will provide the experimental base for the biological treatment of osteosarcoma in the future. Using RT-PCR and Western blot, the results showed that the expression rate of TRAF6 mRNA in osteosarcoma tissues was significantly higher than that in normal bone tissue (p < 0.05), that the expression rate of TRAF6 mRNA in the carcinoma tissues from patients with lung metastasis was significantly higher than that from patients without lung metastasis (p < 0.05), and that the expression rate of TRAF6 mRNA also increased with increasing Enneking stage (p < 0.05). However, the mRNA expression of TRAF6 in osteosarcoma was independent of the patient's gender, age, and tumor size (p > 0.05). The TRAF6 protein displayed an up-regulation in osteosarcoma tissues compared to normal bone tissue (p < 0.05), displayed an up-regulation in osteosarcoma tissues from patients with lung metastasis compared to from patients without lung metastasis (p < 0.05), and displayed a gradual increase with increasing Enneking stage (p < 0.05). By the technique of RNA interference, the expression of TRAF6 in the human osteosarcoma MG-63 cell line was down-regulated, and the invasive ability of MG-63 cells was examined. The results showed that TRAF6 protein expression was significantly decreased in the MG-63 cells from TRAF6 siRNA-transfected group (p < 0.05), and the proliferation ability of MG-63 cells and the number of MG-63 cells that passed through the Transwell chamber were significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). In addition, the percentage of MG-63 cells undergoing apoptosis was significantly higher in the TRAF6 siRNA-transfected group compared with the non-transfected control group as well as the transfected control group (p < 0.05). The expression of p-p65, cyclin D1, MMP-9 was down-regulated in the MG-63 cells from TRAF6 siRNA-transfected group. The expression of caspase 3 was up-regulated in the MG-63 cells from TRAF6 siRNA-transfected group compared to the non-transfected control group as well as the transfected control group (p < 0.05). To make a long story short, the overexpression of TRAF6 in osteosarcoma might be related to the tumorigenesis, invasion of osteosarcoma.Molecular and Cellular Biochemistry 08/2012; 371(1-2). DOI:10.1007/s11010-012-1434-4 · 2.39 Impact Factor
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ABSTRACT: Objective: To investigate the association of downregulated CDH13 expression with invasiveness of bladder transitional cell carcinoma (TCC). Materials and Methods: CDH13 and matrix metalloproteinase-2 (MMP2) expression was detected in 23 normal bladder epithelial tissues and 71 bladder TCC tissues. RNA interference was used to inhibit CDH13 expression in bladder TCC 5637 cells and then analyzed its effects on migration, invasion, adhesion, and proliferation of 5637 cells, as well as MMP2 expression in 5637 cells. Results: The CDH13 expression in bladder TCC tissues was significantly lower than that in normal bladder epithelial tissues. Moreover, the expression of CDH13 from the muscle-invasive group was significantly lower than that from the non-muscle-invasive group. In addition, the MMP2 expression was increased in bladder TCC, especially in muscle-invasive tumors. After the transfection of CDH13 siRNA into 5637 cells, CDH13 expression was significantly decreased, and the migration, invasion, adhesion of 5637 cells, as well as MMP2 expression in 5637 cells was significantly promoted compared with blank and negative controls. Conclusions: Downregulated expression of CDH13 is associated with increased invasion of bladder TCC, and may be due to the enhancement of cell-extracellular matrix adhesion and increased MMP2 expression.Urologia Internationalis 12/2012; 90(2). DOI:10.1159/000345054 · 1.15 Impact Factor