Metastasis-associated Gene 1 Expression Research Articles

Correlation between metastasis-associated gene 1 expression and tumor-associated macrophages in non-small cell lung cancer.

The role of metastasis-associated gene 1 (MTA1) in the metastasis of non-small cell lung cancer (NSCLC) has been proved, but its role in the tumor microenvironment is still insufficient. The study was performed to explore the correlation between MTA1 and tumor-associated macrophages (TAMs) in NSCLC. The expression profile data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were downloaded from TCGA database. The tumor-infiltrating immune cells in each LUAD and LUSC patient were estimated using the CIBERSORT method. Then, the online TIMER database containing multiple algorithms was used to analyze the relationship between MTA1 and TAMs. Besides, correlations between MTA1 and TAMs markers were also explored. Additionally, the immunohistochemistry staining of MTA1 protein and CD206 was performed in 75 NSCLC tissue specimens. Associations of MTA1 and CD206 with the clinicopathological characteristics were analyzed, as well as the correlation between MTA1 and CD206. Based on different algorithms, MTA1 expression was correlated with the distribution of infiltrating immune cells in the tumor microenvironment and negatively correlated with tumor immune-stromal score. MTA1 was associated with TAMs markers according to TCGA database. In 75 NSCLC tissue specimens, the positive rate of MTA1 was 60.00% (45/75), which of CD206 was 42.67% (32/75). The MTA1 expression was significantly correlated with T stage, lymph node metastasis, and TNM stage. The CD206 expression was significantly correlated with T stage, lymph node metastasis, TNM stage, and tumor type. Additionally, we found that MTA1 was positively correlated with CD206 in NSCLC and LUSC. In NSCLC, MTA1 expression was correlated with the infiltrations of different types of macrophages and the expression of TAMs markers, as well as the M2-TAMs marker CD206, suggesting that MTA1-promoting tumor metastasis may mediate the infiltration of different types of macrophages in the tumor microenvironment.

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation.

Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.

Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair.

BackgroundMalignant pleural mesothelioma (MPM) chemoresistance remains a challenge to oncologists. In our previous study, we demonstrated that the aberrant expression of metastasis-associated gene 1 (MTA1) is associated with carcinogenesis and metastasis in MPM. The aim of the present study was to investigate the mechanism of MTA1 and chemo-resistance in MPM.MethodsWestern blotting and real-time polymerase chain reaction were used to analyze the protein and mRNA levels. A stable clone with a knockdown of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Cell Counting Kit-8 assay and crystal violet assay were used to measure cell viability. Immunochemical staining was employed to detect MTA1 expression in MPM tissues. The cell cycle of MPM cells was determined by phosphohistone H3 staining and flow cytometric analysis.ResultsThe MTA1 protein was upregulated and enhanced cisplatin resistance in MPM. Cisplatin stabilized the expression of the MTA1 protein by inhibiting its ubiquitination, and MTA1 enhanced G2/M cell cycle delay and regulated and protected the tumor genome from chemotherapeutic drugs via participating in the phosphorylation of the ataxia telangiectasia mutated and rad3 related-checkpoint kinase 1 (ATR-Chk1) pathway.ConclusionsThese data suggest that MTA1 enhances cisplatin resistance by ATR-Chk1-mediated DNA damage repairment and cisplatin stabilizes MTA1 expression via affecting on the ubiquitination pathway of MTA1 in MPM. Our findings indicate that MTA1 could serve as a novel therapeutic target to overcome chemoresistance in MPM.

Elevated MTA1 induced the migration and invasion of renal cell carcinoma through the NF-\u03baB pathway

BackgroundThe metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC.Methods109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65.ResultsHerein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs.ConclusionsMTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.

Knockdown of MTA1 inhibits the proliferation and apoptosis of esophageal cancer cells

Objective: To investigate the effects of metastasis associated gene 1 (MTA1) expression on the proliferation and apoptosis of human esophageal cancer Eca109 cells. Methods: MTA1 siRNA was transfected into human esophageal cancer Eca109 cells, and the control group and blank group were set up. The expression of MTA1 in Eca109 cells with different treatment was detected by real-time fluorescent quantitative PCR (RT-PCR) and western blot. The proliferation of Eca109 cells was detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The cloning formation ability of Eca109 cells was detected by plate cloning assay. The apoptosis of Eca109 cells were detected by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA) and apoptosis-related proteins, including cleaved caspase-3 and total caspase-3 protein in Eca109 cells were detected by western blot. Results: After 48 hours of transfection, RT-PCR result showed that the relative expression levels of MTA1 mRNA in Eca109 cells in the blank group, control group, and siRNA group were 1.00±0.10, 0.98±0.09 and 0.21±0.03, respectively. The expression of MTA1 mRNA in siRNA group was significantly inhibited (P<0.05), while no significant difference of MTA1 mRNA expression between the blank group and the control group has been found (P>0.05). Western blot results were consistent with those of RT-PCR. MTT array results showed that, compared with the blank group and transfection group, the absorbance values of Eca109 cells in siRNA group were dramatically reduced at 48, 72, and 96 h (all P<0.05). There were no significant differences of absorbance values between the blank group and the control group at 48, 72, and 96 h (all P>0.05). The results of the plate colony formation test showed that the number of colony formation in the blank group and control group were 58.64±6.86 and 60.02±7.04, respectively, significantly higher than 18.10±3.16 in siRNA group (P<0.05), while there was no significant difference between the blank group and control group (P>0.05). Flow cytometry results showed that the apoptosis rates in the blank group and control group were (2.13±0.54)% and (2.27±0.61)%, respectively, significantly lower than (32.61±5.28)% in siRNA group (P<0.05), while there was no significant difference between blank group and control group (P>0.05). Western blot results showed that the expression of PCNA protein was down-regulated while cleaved caspase-3 protein expression was upregulated in siRNA group, compared to the control group and blank group (P<0.05). Conclusions: Inhibition of MTA1 expression can inhibit the proliferation of Eca109 cells and induce apoptosis. This process may be related to the down-regulation of PCNA protein expression and activation of caspase-3 protein expression.

Metastasis-associated protein 1 promotes epithelial-mesenchymal transition in idiopathic pulmonary fibrosis by up-regulating Snail expression.

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually fatal lung disease that lacking effective interventions. It is well known that aberrant activation of transforming growth factor‐beta1 (TGF‐β1) frequently promotes epithelial‐mesenchymal transition (EMT) in IPF. Metastasis‐associated gene 1 (MTA1) has identified as an oncogene in several human tumours, and aberrant MTA1 expression has been related to the EMT regulation. However, its expression and function in IPF remain largely unexplored. Using a combination of in vitro and in vivo studies, we found that MTA1 was significantly up‐regulated in bleomycin‐induced fibrosis rats and TGF‐β1‐treated alveolar type Ⅱ epithelial (RLE‐6TN) cells. Overexpression of MTA1 induced EMT of RLE‐6TN cells, as well as facilitates cell proliferation and migration. In contrast, knockdown of MTA1 reversed TGF‐β1‐induced EMT of RLE‐6TN cells. The pro‐fibrotic action of MTA1 was mediated by increasing Snail expression through up‐regulating Snail promoter activity. Moreover, inhibition of MTA1 effectively attenuated bleomycin‐induced fibrosis in rats. Additionally, we preliminarily found astragaloside IV (ASV), which was previously validated having inhibitory effects on TGF‐β1‐induced EMT, could inhibit MTA1 expression in TGF‐β1‐treated RLE‐6TN cells. These findings highlight the role of MTA1 in TGF‐β1‐mediated EMT that offer novel strategies for the prevention and treatment of IPF.

MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial–mesenchymal transition via the hedgehog signaling pathway

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene in many tumors, and aberrant MTA1 expression has been related to invasion and migration; however, its role and underlying molecular mechanism in oral squamous carcinoma (OSCC) remain largely unexplored. In this work, we determined the expression of MTA1 in OSCC tissues and cell lines. The effect of MTA1 on metastasis and the role of MTA1 in the epithelial-to-mesenchymal transition (EMT) of OSCC cells were evaluated by assays both in vitro and in vivo. We also identified the key Hedgehog signaling pathway-related protein involved in the MTA1-induced EMT. We found that MTA1 expression was upregulated and positively related to the metastasis in OSCC tissues and cell lines. MTA1 overexpression promoted OSCC invasion, migration, and induced EMT, while its silencing had the opposite effect both in vitro and in vivo. Additionally, our data further revealed the relevant molecular mechanism, Hedgehog(Hh) signaling pathway contributed to the effect of MTA1 on the aggressive phenotypes of OSCC cells.These findings indicate that MTA1 enhances OSCC cells invasion and migration by inducing EMT via the Hedgehog signaling pathway, which suggests MTA1 may be an effective anti-OSCC therapeutic target.

Prognostic and clinical significance of metastasis-associated gene 1 overexpression in solid cancers: A meta-analysis.

Background:In the past 2 decades, metastasis-associated gene 1 (MTA1) has attracted attention for its close association with cancer progression and its roles in chromatin remodeling processes, making it a central gene in cancer. The present meta-analysis was performed to assess MTA1 expression in solid tumors.Materials and methods:This analysis identified studies that evaluated the relationship between MTA1 expression and clinical characteristics or prognosis of patients with solid tumors via the PubMed, Cochrane Library, and Embase electronic databases. Fixed-effect and random-effect meta-analytical techniques were used to correlate MTA1 expression with outcome measures. The outcome variables are shown as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI).Results:Analysis of 40 cohort studies involving 4564 cancer patients revealed a significant association of MTA1 overexpression with tumor patient age (>50 vs. <50 years: combined OR 0.73, 95% CI 0.57–0.94), tumor grade (G3/4 vs. G1/2: combined OR 1.94, 95% CI 1.48–2.53), tumor size (>3 cm vs. <3 cm: combined OR 2.35, 95% CI 1.73–3.19), T stage (T3/4 vs. T1/2: combined OR 2.11, 95% CI 1.74–2.56), lymph node metastasis (yes vs. no: combined OR 2.92, 95% CI 2.26–3.75), distant metastasis (yes vs. no: combined OR 2.26, 95% CI 1.42–3.59), TNM stage (III/IV vs. I/II: combined OR 2.50, 95% CI 1.84–3.38), vascular invasion (yes vs. no: combined OR 2.26, 95% CI 1.92–3.56), and poor overall survival time (HR 1.83; 95% CI: 1.53–2.20; P = .000).Conclusions:Our analyses demonstrate that MTA1 was an effective predictor of a worse prognosis in tumor patients. Moreover, MTA1 may play important role in tumor progression and outcome, and targeting MTA1 may be a new strategy for anti-cancer therapy.

Expression of MTA1 in endometriosis and its relationship to the recurrence.

Metastasis-associated gene 1 (MTA1) is correlated with prognosis of many tumors. However, little is known about the role of MAT1 in endometriosis and its relationship with the recurrence of endometriosis.The expression of MTA1 in normal, eutopic and ectopic endometrium was detected by immunohistochemistry and RT-PCR, respectively. The relationship of MTA1 expression with the recurrence of endometriosis was evaluated.In the normal endometrium, eutopic endometrium and ectopic endometrium, the positive rates of MTA1 expression showed a gradually increasing trend. In addition, the MTA1 expression difference between each two groups was significant (P < .0125). However, there was no significant difference between proliferative phase and secretory phase in each group (P > .05). In the ectopic endometrium, MTA1 expression in the severe phases (III-IV) was significantly higher than that in mild phases (I-II) (P < .05), indicating the expression of MTA1 correlates with r-AFS staging (P < .05). Additionally, the MTA1 mRNA level was also closely related to the stages of r-AFS, but not to the proliferative phase or secretory phase of endometrium. Logistic regression analysis showed that r-AFS stage and MTA1 overexpression were risk factors for the recurrence of endometriosis. While, postoperative pregnancy was a protective factor for its relapse.MTA1 is closely associated with the occurrence and development of Ems. Thus, MTA1 level may be used as a new indicator to predict the progression of endometriosis.

MTA1 promotes the invasion and migration of pancreatic cancer cells potentially through the HIF-α/VEGF pathway

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene, and abnormal MTA1 expression has been related to progression of numerous cancer types to the metastasis stage. However, the function of MTA1 in the regulation of pancreatic cancer progression and metastasis remains unclear. Western blot analysis was adopted to determine the expression of MTA1 in pancreatic cancer tissues and corresponding near normal tissues. Steady clone with MTA1-overexpression and MTA1-inhibitionweregenerated via lentivirus technology in BxPc-3 cells. Transwell assay was carried out for detecting the invasion of pancreatic cancer cells. The migration activity was assessed using the wound scratch assay. The effect of MTA1 in pancreatic cancer was evaluated in the mice xenografts. Western blot analysis was employed to determine the expression of hypoxia inducible factor-α (HIF-α) and vascular endothelial growth factor (VEGF) in vitro and in vivo. We observed that MTA1 overexpression enhanced migration and invasion ability of pancreatic cancer cells in vitro and increased HIF-α and VEGF protein levels in vitro and in vivo. MTA1 inhibition had the opposite effects. MTA1 protein level was positively related to HIF-α and VEGF protein levels. These results indicated that MTA1 potentially promoted pancreatic cancer metastasis via HIF-α/VEGF pathway. This research supplies a new molecular mechanism for MTA1 in the pancreatic cancer progression and metastasis. MTA1 may be an effective therapy target in pancreatic cancer.

The protein expression and clinical significance of metastasis-associated gene 1, matrix metalloproteinase-2 and coiled-coil domain containing 67 in papillary thyroid carcinoma

Objective To investigate the expression of metastasis-associated gene 1 (MTA1), matrix metalloproteinase (MMP)-2 and coiled-coil domain containing 67 (CCDC67) proteins in papillary thyroid carcinoma (PTC) tissues and adjacent normal tissues so as to explore their clinical significance in the pathogenesis of PTC. Methods MTA1, MMP-2 and CCDC67 protein expression levels were detected by immunohistochemistry in 61 cases of PTC. A lentiviral expression vector carrying CCDC67 was constructed to obtain an efficient and stable expression of CCDC67 in TPC-1. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the MTA1, MMP-2 and CCDC67 mRNA levels in the cell line of PTC. Results The protein expression rate of CCDC67 in PTC tissue was lower than that in non-cancerous adjacent tissues (49.1% vs. 96.7%), and the expression rate of CCDC67 protein was related to tumor size, TNM stage, pathological grade and lymph node metastasis (χ2=3.911, 7.289, 10.353, 8.826, P=0.048, 0.007, 0.001, 0.003). The protein expression rate of MTA1 and MMP-2 in PTC tissues was higher than that in non-cancerous adjacent tissues (63.9% vs. 18.0%, 62.3% vs. 14.8%), and the expression rate of MTA1 and MMP-2 protein was related to PTC in TNM stage, pathological grade and lymph node metastasis (χ2=6.213, 12.752, 4.665, P=0.013, 0.000, 0.031; χ2=5.026, 5.026, 6.036, P=0.025, 0.025, 0.014). The expression levels of MTA1 and MMP-2 proteins both displayed a correlation to the expression of CCDC67 protein (χ2=7.634, r=0.334, P=0.006; χ2=6.139, r=0.302, P=0.013). There was obvious mRNA expression of MTA1 and MMP-2 in PTC cell line, and there was no detectable expression of CCDC67. The expression levels of MTA1 and MMP-2 mRNA in NC and CON groups were relatively down-regulated as compared with OE group. Conclusion The expression levels of MTA1, MMP-2 and CCDC67 were associated with the matastasis and invasion of PTC. As a tumor suppressor gene, CCDC67 may play an important role in the matastasis and invasion of PTC by inhibiting the expression of MTA1 and MMP-2. Key words: Papillary thyroid carcinoma; Metastasis-associated gene 1; Matrix metalloproteinase-2; Coiled-coil domain containing 67

Clinical Significance and Phenotype of MTA1 Expression in Esophageal Squamous Cell Carcinoma.

Metastasis-associated gene 1 (MTA1) is considered a potential prognostic factor in esophageal cancer. We investigated the clinical relationship between MTA1, LAT1, and tumor metabolism, as evaluated by positron emission tomography (PET) in esophageal squamous cell carcinoma. We analyzed 142 esophageal squamous cell carcinoma patients who underwent curative resection without preoperative treatment. MTA1 expression was assessed by immuno-zahistochemistry, and tested against standardized uptake values from preoperative PET-CT. The association among MTA1, LAT1, and 18FAMT PET results were analyzed. MTA1 staining was observed in 82 of 142 cancer tissues. Five-year overall survival was 69.9 % in the absence of MTA1, but 50.7% otherwise (p=0.021), while disease-free survival was 66.5% and 49.0% (p=0.071), respectively. Abnormal 18FAMT accumulation was noted in 13 patients without MTA1 and in 18 patients with MTA1 (p=0.079), with maximum standardized uptake value 1.6±1.6 and 2.7±1.6, respectively (p=0.036). MTA1 expression was positively correlated with LAT1 (p=0.013) and CD34 (p=0.034) expression, but not with Ki-67 (p=0.078). MTA1 shows promise as a diagnostic and prognostic marker in esophageal cancer, and we anticipate that the gene will also prove to be a good therapeutic target.

Clinicopathological Significance of MTA 1 Expression in Patients with Non-Small Cell Lung Cancer: A Meta-Analysis

Background:Metastasis associated gene 1(MTA1) is one of the most deregulated molecules in human cancer and leads to cancer progression and metastasis. We performed a meta-analysis to determine the correlations between MTA1 expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC).Methods:We searched PubMed, Springer, Science Direct, Google Scholar and China National Knowledge Infrastructure (CNKI) for relevant articles. For statistical analyses, we used R3.1.1 software. The fixed or random effects model was employed based on the results of the statistical test for homogeneity.Results:Seven studies involving 660 NSCLC patients were included. The proportion of MTA1 overexpression with 95% confidence interval (95% CI) was 0.53(95% CI: 0.43-0.62) in NSCLC patients; 0.47(95% CI: 0.40-0.55) in age <60 years and 0.52(95% CI: 0.34-0.70) in age ≥60 years; 0.5(95% CI: 0.41-0.62) in males and 0.51(95% CI: 0.39-0.62) in females; 0.59(95% CI: 0.48-0.69) in squamous cell carcinoma (SC) and 0.57(95% CI: 0.46-0.67) in adenocarcinoma (AC); 0.39(95% CI: 0.23-0.56) in well-differentiated tumors, 0.44(95% CI: 0.37-0.51) in moderately differentiated tumors and 0.55(95% CI: 0.37-0.51) in poorly differentiated tumors; 0.48(95% CI: 0.36-0.60) in clinical grade (III-IV) NSCLC and 0.75 (95% CI: 0.69-0.81) in clinical grade (I-II) NSCLC; 0.58(95% CI: 0.45-0.71) in T Stage (T1/T2) NSCLC; 0.68(95% CI: 0.49-0.82) in NSCLC patients with lymph node positivity and 0.51(95% CI: 0.43-0.58) in NSCLC patients with lymph node negativity.Conclusions:These results indicated that MTA1 might be a valuable biomarker in the diagnosis of NSCLC. MTA1 overexpression was significantly associated with age ≥60 years, gender, histopathological type, clinical grade (I-II), T stage (T1/T2) and lymph node positivity in NSCLC patients.

MicroRNA-30c inhibits metastasis of ovarian cancer by targeting metastasis-associated gene 1.

It is important to find reliable molecular markers or biological targets that associate with ovarian cancer (OC) metastasis for diagnosis and treatment. In this study, researchers investigated the regulated chain of microRNA-30c (miR-30c) and metastasis-associated gene 1 (MTA1) in OC tissues and cells. Expression of miR-30c and MTA1 was detected with quantitative real-time polymerase chain reaction and immunohistochemistry in 33 OC and matched adjacent tissues. MiR-30c mimics were synthetized and transfected into SKOV3 cells to target MTA1. The wound healing and transwell assays were detected to observe migration and invasion of transfected OC cells. Compared with matching normal ovarian tissues, the MTA1 expression was upregulated and localized in the cytoplasm, and the expression of miR-30c was significantly reduced. The expression intensity of MTA1 was correlated with the Federation of Gynecology and Obstetrics stage, tumor grade, and metastasis of OC. Transfecting miR-30c mimics could significantly reduce the expression of MTA1 in SKOV3 cells and obviously inhibit the migration and invasion of SKOV3 cells. MiR-30c and MTA1 abnormally expressed in OC, which may be related to metastasis of OC. In MiR-30c as a tumor suppressor gene, its expression in OC could lead to reduced expression of MTA1, which may be one of the mechanisms of metastasis of OC cells.

Metastasis-associated gene 1 expression in human medulloblastoma and its association with invasion and metastasis in medulloblastoma Daoy cell lines.

This study aims to investigate the expression of metastasis-associated gene 1 (MTA1) in human medulloblastoma, and its significance in the invasion and metastasis in a medulloblastoma cell line. Positive expression rate of MTA1 protein in medulloblastoma and adjacent normal tissues collected from 29 medulloblastoma patients was detected by immunohistochemistry assay in vivo. In in vitro experiments, Daoy cells were transfected with MTA1-targeted small interfering RNA (siRNA, MTA1-siRNA group), niRNA (MTA1-niRNA group), and plasmid vectors (control group). Transfection efficiency was evaluated by PT-PCR and western blot; cell adhesion, migration, and invasion capacity was assessed by adhesion assays, scratch assays, and transwell chamber invasion assays, respectively. Results indicated that the positive expression rate of MTA1 protein in the medulloblastoma tissues was higher as compared with that of the adjacent normal tissues (P < 0.05). In addition, mRNA and protein expression of MTA1 in the MTA1-siRNA group was lower than that in the control and MTA1- niRNA groups (P < 0.05). Adhesion, migration, and invasion capacity of Daoy cells in the MTA1-siRNA group was inhibited as compared with the control and MTA1-niRNA groups (P < 0.05). In conclusion, MTA1 expression was increased in medulloblastoma cells, while MTA1 knockdown in medulloblastoma cells inhibited MTA1 expression. In addition, MTA1 knockdown inhibited the adhesion, migration, and invasive capabilities of medulloblastoma cells. It is possible that MTA1 can serve as a biomarker and a potential therapeutic target for medulloblastoma.

MTA1 promotes metastasis of MPM via suppression of E-cadherin.

BackgroundMetastasis-associated gene 1(MTA1) has been identified as an oncogene in many tumors, and aberrant MTA1 expression has been linked to carcinogenesis and metastasis. We aim to investigate the mechanism of MTA1 and metastasis in malignant pleural mesothelioma (MPM).MethodsReal-time polymerase chain reaction (PCR) and immunohistochemical staining were employed to detect MTA1 and E-cadherin expression in MPM tissues and corresponding adjacent tissues. Stable clone with knock-down of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Wound-healing assay, transwell assay and PCR array were carried out for detecting invasion and migration of MPM cells. Luciferase reporter assay was performed to validate the effect of MTA1 on E-cadherin.ResultsMTA1 expression is up-regulated in MPM and shown a negative correlation with E-cadherin expression. MTA1 could enhance the invasion and migration of MPM cells via suppressing the expression of E-cadherin. MTA1 overexpression is associated with pathology, metastasis and survival rate of MPM patients.ConclusionsMTA1 plays an important role in Epithelial-to-mesenchymal transition (EMT) to promote metastasis via suppressing E-cadherin expression, resulting in a poor prognosis in MPM. MTA1 is a novel biomarker and indicative of a poor prognosis in MPM patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0269-8) contains supplementary material, which is available to authorized users.

MiR-125a-3p targets MTA1 to suppress NSCLC cell proliferation, migration, and invasion.

Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3'-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2'-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets.

Hypoxia-induced MTA1 promotes MC3T3 osteoblast growth but suppresses MC3T3 osteoblast differentiation.

BackgroundBone fracture is one of the most common physical injuries in which gene expression and the microenvironment are reprogramed to facilitate the recovery process.MethodsBy specific siRNA transfection and MTT assay, we evaluated the effects of metastasis-associated gene 1 (MTA1) in osteoblast growth. To show the role of MTA1 in osteoblast under hypoxia conditions, by overexpressing and silencing MTA1 expression, we performed mineral deposition and alkaline phosphatase activity assay to observe the differentiation status of osteoblast cells. Real-time PCR and Western blot assays were adopted to detect the expression of certain target genes.ResultsHere, we reported that hypoxia-induced MTA1 expression through hypoxia-induced factor 1 alpha (HIF-1α) and stimulated the growth of osteoblast MC3T3 cells. Silencing of MTA1 through specific siRNA suppressed MC3T3 cell growth and elicited cell differentiation and induced alkaline phosphatase activation and the upregulation of bone morphogenetic protein-2 and osteocalcin.ConclusionsWe found that MTA1 was regulated by HIF-1α in hypoxia circumstance to suppress osteoblast differentiation. These findings provide new insights for bone fracture healing and new strategies to develop potential targets to promote fracture healing.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-015-0084-x) contains supplementary material, which is available to authorized users.

Metastasis associated protein 1 correlates with Hypoxia inducible-factor 1 alpha expression and lymphangiogenesis in esophageal cancer.

Metastasis to regional lymph nodes represents the first step of dissemination in esophageal cancer and serves as an unfavorable prognostic indicator for disease progression. The formation of tumor lymphatic microvessels is dependent on the production of lymphangiogenic growth factors by tumor cells, such as vascular endothelial growth factor C (VEGF-C), metastasis-associated gene 1 (MTA1), and hypoxia inducible-factor l alpha (HIF-1α). The degree of intratumoral lymphatic microvessel density (LMVD) by immunohistochemistry is thought to influence tumor lymph node metastasis (LNM) and prognosis in various solid tumors. The aim of this study was to investigate the expression of MTA1 and HIF-1α in human esophageal cancer and to explore the relationship between their expression and lymphangiogenesis. The expression of MTA1 and HIF-1α, and LMVD marked by D2-40 were detected using immunohistochemical staining in eighty-two human esophageal cancer cases. The positive rates of MTA1 and HIF-1α expression were 69.5% and 59.8%, respectively. The expression of MTA1 and HIF-1α were both correlated with LNM. In addition, MTA1 and HIF-1α expression has a positive correlation in human esophageal cancer; LMVD correlated significantly with LNM. LMVD in MTA1 and HIF-1α over-expression cases was higher than that in none or weak cases, and this difference has statistical significance. Our findings suggest that MTA1 plays an important role in lymphangiogenesis and LNM by stabilizing HIF-1α in esophageal cancer. The inhibition of lymphangiogenesis, MTA1, or HIF-1α activity may have an important therapeutic benefit in the control of esophageal cancer.

Metastasis-associated protein 1 is a novel marker predicting survival and lymph nodes metastasis in cervical cancer

Metastasis-associated gene 1 (MTA1), which is involved in tumor progression, metastasis, and angiogenesis, has been examined in several malignant tumors. However, the expression and the effect of MTA1 on human cervical cancer remain unknown. In this study, we investigated the level of MTA1 expression in cervical carcinoma and its clinical significance. By immunohistochemical staining, the correlation of MTA1 overexpression with clinical features and patient outcome was analyzed in 132 formalin-fixed, paraffin-embedded cervical cancer tissues. MTA1 protein overexpression was detected in 73 (55.3%) of 132 patients. High levels of MTA1 protein were clearly correlated with histologic grade (P = .006), lymph node metastasis (P = .001), and recurrence (P = .016). Multivariate Cox analysis showed that MTA1 was an independent factor for overall survival (hazard ratio, 3.486; 95% confidence interval [CI], 1.274-9.537; P = .015) and disease-free survival (hazard ratio, 3.373; 95% CI, 1.212-9.387; P = .020). Multivariate logistic regression analysis indicated that elevated MTA1 was strongly associated with lymph node metastasis (odds ratio, 3.879; 95% CI, 1.391-10.816; P = .010). Sensitivity and specificity were calculated as 81.25% and 53.0%, respectively. These findings suggest that MTA1 nuclear overexpression is associated with tumor progression and metastasis and thus support its clinical significance in future gene-targeted therapies, particularly the management of patients with cervical cancer.