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Introduction: Burkitt’s lymphoma is a high-grade B-cell neoplasm and one of the most aggressive malignancies of lymphoid origins which found mainly in the paediatric population. The treatment options of this tumour are still limited. However, a new strategy for refractory tumour, phosphorothioate oligonucleotide antisense technique has watched with keen interest. This study was aimed to examine the effect of antisense p45Skp-2 (Skp-2 AS) suppressed migratory chemotactic and metastasis of oral malignant Burkitt’s lymphoma (Raji) cell through down-regulation of MTA-1 and E-cadherin. Methods: True experiment laboratory with post-test control group design was confirmed in this study. The efficiency of Skp-2 AS in the suppression of cell chemotactic migration was examined by Boyden chamber assay. To evaluate the inhibition of cell metastasis was conducted by decreasing MTA-1 expression protein. The expressions of MTA-1, E-cadherin and α-tubulin protein were investigated by Western blot analysis. Results: The results revealed that the number of chemotactic migration of Skp-2 AS treated Raji cell was significantly decreased when compared with that of sense p45Skp-2 (Skp-2 S) and scrambled control (SC) cells (P

Aim: To examine the decreased of metastatic associated protein-1 (MTA-1), complex of cyclin-dependent kinase-2 (CDK2)--cyclin E, and nuclear factor-kappa beta (NF-ĸB) expression as a molecular target therapy of oral Burkitt's lymphoma (Raji) cells mediated by oligonucleotides KIP-1 sense (KIP-1 S) and SKP-2 antisense (SKP-2 AS). Materials and Methods: In the study, the pure laboratory experimental with posttest only control group design was confirmed. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2Htetrazolium bromide] assay was performed to evaluate the suppression of cell growth. The chemotactic migration activity was carried out by Boyden chamber assay. Activation of MTA-1, NF-ĸB, cyclin E, CDK2, SKP-2, KIP-1, and α-tubulin was investigated by Western blot analysis. Apoptosis cells were analyzed by caspase-3 and caspase-9. Results: The growth inhibition and chemotactic migration activity of KIP-1 S and SKP-2 AS cells were significantly inhibited when compared with the scrambled control (SC) cells. Interestingly, Raji-KIP-1 S has potentially greater cell growth and migrated chemotactic suppression than SKP-2 AS. Induction of cell apoptosis was confirmed in KIP-1 S and SKP-2 AS proofed by increasing the activation of caspase-3 and caspase-9. Decreased level of MTA-1, NF-ĸB, cyclin E, CDK2, SKP-2, and increased level of KIP-1 protein were detected in KIP-1 S- and SKP-2 AS-treated cells. Conclusion: KIP-1 S and SKP-2 AS have strong antitumor activity on the oral Burkitt's lymphoma cells through downregulation of MTA-1, CDK2--cyclin E complex, and NF-kB expression. However, KIP-1 S had a stronger antitumor activity than SKP-2 AS targeting these molecules could represent a promising new therapeutic approach for this type of tumor. [ABSTRACT FROM AUTHOR]

Burkitt's lymphoma (BL) is an uncommon type of Non-Hodgkin lymphoma (NHL). It is a highly aggressive type of B-cell lymphoma and the most common childhood cancer. Treatment for this cancer is still limited. However, a new strategy for refractory tumor, gene therapy is watched with keen interest. The aim of study was to investigate the expression of non-metastatic 23 (nm-23) and metastatic associated protein-1 (MTA-1) of an oral malignant Burkitt's lymphoma induced by oligonucleotide p27 sense (p27 S). The true experimental study with post-test only control group design was confirmed in this study. For detection of nm-23, MTA-1, p27Kip-1 and a- tubulin protein expressions were carried-out by Western blotting analysis. Induction of apoptosis was analyzed by double staining using acridine orange-ethidium bromide (AO-EB). Results revealed the expression of nm-23 and p27Kip-1 protein was markedly increased in cell transfected with p27 sense. Contrally, down regulation of MTA-1 protein was detected in these cell transfectant. Apoptosis induction was significantly elevated in Raji-p27 S compared with that of p27 AS. In conclusion, oligonucleotide p27 S has a strong antitumor activity in oral malignant Burkitt's lymphoma through increasing the apoptosis activity, expression of nm-23 and p27Kip-1 protein induction, and suppressing the expression of MTA-1 protein targeting this molecule could represent a promising new therapeutic approach for this type of cancer. [ABSTRACT FROM AUTHOR]

Abstract Ninety percent of all cancer related deaths happen due to metastatic progression. One important protein facilitating metastatic progression in hepatocellular carcinoma (HCC) is the metastasis associated 1 protein (MTA-1). We have earlier shown that in the context of HCC and normal liver cell lines, HuH6 and THLE-2, respectively. MTA-1 protein is actively stabilized in HCC cell lines and actively degraded in normal liver cells. We had also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1 protein in normal liver cells. However, the exact mechanism by which TRIM25 degrades MTA-1 protein has still not been elucidated. In the study, we used both in situ prediction algorithms and mass spectrometry based post-translational modification analysis to map the lysine residues in MTA-1 that are polyubiquitinated. Whereas UbPred algorithm revealed a combination of medium and low confidence sites, it revealed only one high confidence lysine (K98) residue. The hCKSAAP_UbSite algorithm also predicted K98 site. Mass spectrometry analysis also showed that K98 has ubiquitin modification. Immunofluorescence analysis showed that in normal liver cell line, THLE-2, which has high expression of TRIM25, ectopically expressed FLAG-tagged wild-type MTA-1 was actively degraded, but the K98R mutant MTA-1 was not. In vitro ubiquitination assay using recombinant wild-type and K98R mutant MTA-1 confirmed that MTA-1 is poly-ubiquitinated at K98 residue by TRIM25. The K98R mutant had a longer half-life than wild-type MTA-1 protein in an in vitro protein stability assay. We establish that TRIM25 ubiquitinates MTA-1 at lysine 98 and degrades it normal liver cells. [ABSTRACT FROM AUTHOR]

Tumor metastasis accounts for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) considered to be centrally important in acquired resistance to chemotherapy and in progression of tumors to secondary organs. One of the important mediators of metastatic progression in hepatocellular carcinoma (HCC) is the metastasis associated protein 1 (MTA-1). We have earlier shown that in the context of HCC and normal liver cell lines, MTA-1 protein is actively stabilized in HCC cell lines and actively degraded in normal liver cells. We have also shown that TRIM25 is the E3 ligase that interacts with and degrades MTA-1 protein. The identity of the factor regulating expression of TRIM25 in normal liver cells and HCC is unknown. In the current work we elucidate that microRNA (miR)− 873 targets TRIM25 in HCC cells. Both metagenomic analysis and quantification of miR-873 and TRIM25 in 25 HCC patients revealed an inverse correlation between the two in HCC patients with high miR-873 and low TRIM25 expression, respectively. The expression pattern was mimicked in the normal liver cells THLE-2 and the HCC cell line, HuH6. In vitro luciferase reporter assays confirmed TRIM25 as the target of miR-873. Transient transfection of HuH6 cells with an anti-miR-873 antagomir significantly decreased both transwell motility in these cells. Furthermore, in in vivo xenograft assays treatment with anti-miR-873 antagomir significantly decreased hepatic nodules formation. Cumulatively, our data indicate that suppression of TRIM25 expression by high levels of miR-873 dictates MTA1 protein upregulation in HCC. [ABSTRACT FROM AUTHOR]

The clear cell renal cell carcinoma (ccRCC) is one of the most fatal urologic tumors, and the prognosis remains very poor for advanced or metastatic ccRCC. This study reveals the roles of microRNA (miR)-30c in regulating a highly aggressive ccRCC cell line proliferation by targeting MTA-1, which is a key mediator for human cancer metastasis. Results from quantitative real-time polymerase chain reaction showed that the expression of MTA-1, the target of miR-30c, was significantly higher in metastatic ccRCC specimens than in nonmetastatic ccRCC or nontumor specimens. Accordingly, endogenous miR-30c is at a much lower level in highly aggressive ccRCC Caki-1 cells than nontumor or ccRCC cell lines. Expression of miR-30c via lentivirus vector inhibits the proliferation, anchorage-independent growth, in vitro invasion or migration, or in vivo growth of Caki-1 cells by repressing MTA-1 protein expression. miR-30c also enhances the sensitivity of Caki-1 cells to anticancer agents, including sorafenib and paclitaxel. These data reveal the potential application of miR-30c and that its targeting gene, MTA-1, would be a potential target in metastatic ccRCC treatment. [ABSTRACT FROM AUTHOR]

HER-2/neu overexpression and/or gene amplification occurs in several human malignancies, frequently correlates with tumor aggressiveness, and provides the basis for treatment with trastuzumab. Among neuroendocrine neoplasms (NEN) of the gastroenteropancreatic (GEP) tract, ileal neuroendocrine tumors show peculiar features of malignancy with frequent metastases at the diagnosis. We investigated the overexpression and/or amplification of HER-2/neu and the involvement of the metastasis-related proteins c-Met, MTA-1, and VEGF in 24 primary ileal NEN by immunohistochemistry and fluorescence in situ hybridization (FISH). Data were compared with those of 43 GEP endocrine tumors of other sites. All primary ileal NEN showed an intense membranous and cytoplasmic immunostaining for HER-2/neu. According to the breast cancer scoring system, 17% of ileal carcinoids showed a score of 3+ and 71% with a score of 2+ with a significant difference respect the non-ileal GEP endocrine tumors (p < 0.0000). FISH analysis revealed chromosome 17 polysomy in 33% of 2+/3+ ileal tumors but not HER-2/neu gene amplification. The c-Met and MTA-1 but not VEGF were overexpressed in almost all ileal NEN, whereas VEGF presented more frequently a normal staining. The comparisons with the other GEP NEN demonstrated significant differences for all the three proteins (p < 0.0000, p < 0.0002, and p < 0.001, respectively). These findings suggest that in ileal NEN, HER-2/neu overexpression plays a role in the carcinogenetic process and by triggering the altered expression of c-Met and MTA-1, may activate the molecular pathway(s) promoting tumor progression and metastasis development. Ileal HER-2/neu overexpressing neuroendrocrine tumors may constitute potential candidates for target therapy with specific humanized monoclonal antibodies. [ABSTRACT FROM AUTHOR]

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in non-small cell lung cancer (NSCLC). Expression of MTA1 messenger RNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 74 non-small cell lung carcinoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage II–IV NSCLC (3.465±3.675) was significantly higher than the level in stage I NSCLC (1.614±2.434, P=0.0153). MTA1/GAPDH mRNA levels in T4 NSCLC (4.377±4.169) was significantly higher than the level in T1 NSCLC (1.966±2.148, P=0.0351) and in T2 NSCLC (2.048±1.899, P=0.0269), respectively. MTA1/GAPDH mRNA level in NSCLC with lymph node metastasis (4.242±3.758) was significantly higher in NSCLC without lymph node metastasis (P=0.0169). Our results show that the expression of the MTA1 gene is closely related to invasiveness and metastasis in NSCLC. The gene MTA1 could thus potentially provide information on the mechanism of cancer invasion and metastasis. [Copyright &y& Elsevier]

β-elemene, a non-cellular antineoplastic agent, may be used to effectively inhibit the growth and proliferation of various types of tumor cells by inhibiting the nucleic acid synthesis or inducing their apoptosis and differentiation. The aim of this study was to investigate the expression, as well as the effects, of Mta-1, survivin and Bcl-xL in T24 bladder cancer cells following β-elemene treatment. The expression of the three proteins in T24 cells following β-elemene treatment was analyzed by immunocytochemistry staining and western blot analysis. The survival rate and apoptosis of T24 cells following β-elemene treatment was detected by MTT assay and TUNEL staining. We analyzed the internal corelations between apoptosis-associated genes, tumor metastasis-associated genes (cancer genes) and cell apoptosis, and investigated the mechanism of action by which β-elemene induces the apoptosis of T24 cells at a molecular level. These results provide scientific evidence for further study on the anticancer effect of β-elemene in carcinoma of the urinary bladder. In this study, it is shown that β-elemene downregulates the expression of survivin, Bcl-xL and Mta-1 in tumor cells. The apoptosis of T24 cells is dependent on the dosage and length of incubation time of β-elemene.