ABSTRACT
Objective To investigate the expression of metastasis associated gene-1 (mag-1) and mammalian target of rapamycin (mTOR) in rectal cancer, and its correlation with clinical pathology. Methods The expressions of mag-1 and mTOR in 60 rectal cancer tissue, 30 adenoma tissues and 10 normal rectal tissues were detected by immunohistochemical method, and the correlation between the expression levels and rectal cancer clinical pathologic characteristics was discussed. Results The positive expression rates of mag-1 and mTOR in rectal cancer tissue were significantly higher than those in normal rectal tissue and adenoma tissue:55%(33/60) vs. 1/10 and 27%(8/30), 58%(35/60) vs. 2/10 and 30% (9/30), and there were statistical differences (P 0.05). The correlation analysis result showed that the expressions of mag-1 and mTOR were positively correlated in rectal cancer tissue (r=0.730, P<0.01). Conclusions The mag-1 and mTOR may correlate with invasion and metastasis in rectal cancer, and monitoring mag-1 and mTOR expression has a certain value for determining biological behavior of rectal cancer.
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Objective To analyze the clinical significance of MTA1 overexpression in cervical cancer and bioinformatically screen the potential treatment targets from the gene network correlated with MTA1 overexpression. Methods SPSS software package was used to analyze the correlation of MTA1 with clinical metastasis and pathological grade of cervical cancer based on TCGA-CESC data set. The edgeR software was used to screen the gene set whose expression was correlated with MTA1 in cervical cancer at a global transcriptional level. DAVID platform was adopted to identify the enriched biological functions of the gene set significantly correlated with MTA1 expression. The transcriptional regulation network of the gene set was constructed with STRING online platform and Cytospace softwares to identify the key regulators. Results TCGA-CESC database assay showed a significant positive correlation of MTA1 expression with clinical metastasis of cervical cancer (P<0.01). There was a gene set in which gene expression was closely correlated with MTA1 level. Functional enrichment of the gene set indicated that cancer pathways, stem cell pathways, cell migration, cell differentiation, etc. were closely linked to MTA1-correlated malignant behaviors of cancers. Bioinformatical screening showed that Agt, Acta1, Fpr2, Pmch and RGS18, which are correlated with MTA1 expression in cervical cancer, were the key regulators in differentially expressed gene sets. And these genes were located to the GPCR pathway. Conclusions MTA1 overexpression is significantly correlated with clinical metastasis of cervical cancer and paralleled with the activation of gene regulation involved in stem cell pathway, cytokine receptor signaling, cell migration and differentiation pathways. These genes are correlated with MTA1 expression and potential treatment targets in cervical cancer and should be further experimentally evaluated in the future.
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Objective To explore the effect and mechanism of metastasis associated gene 1 (MTA1) on epithelial-mesenchymal transition(EMT) of esophageal squamous cell carcinoma(ESCC).Methods Lentivirus infection method was used to establish the MTA1 knocking out cell line (LV3-shMTA1-KYSE410) and the MTA1 overexpressing cell line (LVS-MTA1-KYSE450).Western Blot was used to measure the expression of MTA1 and the proteins associated with EMT process.Furthermore,the expression and localization of E-cadherin and Vimentin were observed by immunofluorescence assay under confocal microscope.Finally,the wound healing method was performed to confirm the changes of migration ability of the established cell lines.Results When KYSE-450 cells were overexpressed MTA1,the expression level of E-cadherin was down-regulated while Vimentin was up-regulated,and the migration ability was enhanced (0.91 ± 0.00 vs.0.23 ± 0.04,P ＜0.05).When MTA1 was knocked out in KYSE-410 cells,the results were the opposite (0.19±0.01 vs 0.53±0.01,P ＜0.05).Conclusion Overexpression of MTA1 may promote the process of epithelial-mesenchymal transition and enhance the migration ability of ESCC.
ABSTRACT
It has been reported that metastasis-associated gene 1 (Mtal) is overexpressed in many malignant tumors with high metastatic potential.In addition,some studies indicated that MTA1 participated in invasion,metastasis,and survival of cancer cells by regulating cell migration,adhesion and proliferation.But the role of MTA 1 is unclear in vitro in the development of cervical cancer cells.This study investigated whether and how MTA1 mediated cell proliferation,migration,invasion and adhesion in cervical cancer.MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials.The effects of MTA1 expression on SiHa cell apoptosis,cycle,proliferation,migration,invasion and adhesion were tested by flow cytometry,MTT,wound-healing assay,Transwell assay and adhesion assay,respectively.The expression levels of p53,E-cadherin,and β-catenin activity were evaluated in untreated and treated cells.The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa,which was correlated well with the potential of migration and invasion in both cell lines.Furthermore,the cell invasion,migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mtal-siRNA transfection in SiHa.However,no significant differences were found in cell apoptosis,cycle,and proliferation.In addition,E-cadherin and p53 protein levels were significantly up-regulated,while β-catenin was significantly down-regulated in SiHa transfected with the siRNA.These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells.It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53,and E-cadherin/β-catenin complex.MTA1 could serve as a potential therapeutic target in cervical cancer.