Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic s... more Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic stem cell maintenance, and tumor progression. It also participates in multiple cell signaling pathways including Wnt, Notch, and TGF-β. Remarkably, it is expressed in cancer stem cell (CSC) compartments, boosting tumor cell migration, invasion, and angiogenesis. Although Cripto-1 is overexpressed in a variety of human malignant tumors, its expression in esophageal squamous cell carcinoma (ESCC) remains unclear. Our aim in this study was to evaluate the possible oncogenic role of Cripto-1 in ESCC progression and elucidate its association with clinicopathological parameters in patients. In this study, Cripto-1 expression in 50 ESCC tissue samples was analyzed and compared to corresponding margin-normal esophageal tissues using quantitative real-time PCR. Cripto-1 was overexpressed in nearly 40% of ESCC samples compared with normal tissue samples. Significant correlations were observed betwe...
Evading apoptosis is one of the major hallmarks of cancer cells. Inhibitors of apoptosis (IAPs) p... more Evading apoptosis is one of the major hallmarks of cancer cells. Inhibitors of apoptosis (IAPs) proteins are considered as a most important gene families involved in apoptosis. BRUCE protein, a member of IAPs, is able to quench apoptosis as well as playing role in cell division. Our aim in this study was to analyze BRUCE protein expression in gastric carcinoma (GC) and its correlation with the clinicopathological features. Using immunohistochemistry, 52 GC specimens were studied for BRUCE protein expression. A validated scoring method was applied. BRUCE protein expression was detected in majority of tumor tissues (98.07 %). A significant correlation between gender and BRUCE expression (p = 0.024) was detected. Indeed, females showed higher level of BRUCE expression than male patients. Since specific expression of BRUCE protein was revealed in majority of GC tissues, BRUCE protein may be a useful therapeutic target for cancer therapy. Furthermore, based on the native role of BRUCE protein in inhibition of apoptosis, using this protein in targeted therapy of tumor cells may help to inhibit tumor cells growth and survival leading to rapid elimination of tumor mass.
There is an inevitable association between cell signaling pathways and tumorigenesis. Wnt and not... more There is an inevitable association between cell signaling pathways and tumorigenesis. Wnt and notch pathways play important roles during development and self-renewal. Beside the independent role of such pathways on tumor progression, different cross talks between these pathways through tumorigenesis are emphasized. In this study, we analyzed cross talk between Wnt and NOTCH signaling pathways through assessment of probable correlation between MAML1 and PYGO2 as the main transcription factors of these pathways, respectively in esophageal squamous cell carcinoma (ESCC) patients. Levels of MAML1 and PYGO2 mRNA expression in 48 ESCC patients were compared to the correlated margin normal tissues using real-time polymerase chain reaction (PCR). Eleven out of 48 patients (22.9 %) have shown the concomitant MAML1/PYGO2 over expression in significant correlation with tumor size (p = 0.046) and depth of tumor invasion (p = 0.050). We showed that there is a significant correlation and feedback between these markers during the ESCC progression and metastasis.
Iranian Journal of Basic Medical Sciences, Nov 1, 2014
Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes ... more Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs) are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR). Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line) compared with normal esophageal tissue of ESCC patients. Rate of transfection in KYSE30 was also between 40 to 50%, using the pSilencer-Brg1shRNA (1:1 ratio). Our data indicated that chromatin remodeling machinery is a novel aspect in tumor biology of ESCC, and overexpression of Brg1 as an important member of SWI/SNF might be involved in the migration and invasion of ESCC tumoral cells.
Developmental pathways such as Wnt and Notch are involved in different cellular functions from th... more Developmental pathways such as Wnt and Notch are involved in different cellular functions from the cell cycle regulation to self-renewal. Therefore, aberrations in these pathways may cause tumorigenesis. Msi1 has a critical regulatory role for the Wnt and Notch pathways. In the present study, we have assessed the probable correlation between the Msi1 and MAML1 in esophageal squamous cell carcinoma (ESCC) progression and metastasis. Levels of Msi1 and MAML1 mRNA expression in 51 ESCC patients were compared to the normal tissues using real-time polymerase chain reaction (PCR). Nine out of 51 (17.6 %) cases had Msi1/MAML1 overexpression, and there was a significant correlation between such overexpressed cases and tumor location (p = 0.013). We showed that there is not any direct correlation and feedback between the Msi1 and MAML1 in ESCC patients.
Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes ... more Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs) are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR). Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line) ...
Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, a... more Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21. In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR). Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035). Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.
Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stabilit... more Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects. Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter. It was observed that, 12 out of 39 cases (23.5%) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4%, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p = 0.028) and location (p = 0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis. The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer.
Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic s... more Human Cripto-1, a member of the EGF-CFC family, is involved in embryonic development, embryonic stem cell maintenance, and tumor progression. It also participates in multiple cell signaling pathways including Wnt, Notch, and TGF-β. Remarkably, it is expressed in cancer stem cell (CSC) compartments, boosting tumor cell migration, invasion, and angiogenesis. Although Cripto-1 is overexpressed in a variety of human malignant tumors, its expression in esophageal squamous cell carcinoma (ESCC) remains unclear. Our aim in this study was to evaluate the possible oncogenic role of Cripto-1 in ESCC progression and elucidate its association with clinicopathological parameters in patients. In this study, Cripto-1 expression in 50 ESCC tissue samples was analyzed and compared to corresponding margin-normal esophageal tissues using quantitative real-time PCR. Cripto-1 was overexpressed in nearly 40% of ESCC samples compared with normal tissue samples. Significant correlations were observed betwe...
Evading apoptosis is one of the major hallmarks of cancer cells. Inhibitors of apoptosis (IAPs) p... more Evading apoptosis is one of the major hallmarks of cancer cells. Inhibitors of apoptosis (IAPs) proteins are considered as a most important gene families involved in apoptosis. BRUCE protein, a member of IAPs, is able to quench apoptosis as well as playing role in cell division. Our aim in this study was to analyze BRUCE protein expression in gastric carcinoma (GC) and its correlation with the clinicopathological features. Using immunohistochemistry, 52 GC specimens were studied for BRUCE protein expression. A validated scoring method was applied. BRUCE protein expression was detected in majority of tumor tissues (98.07 %). A significant correlation between gender and BRUCE expression (p = 0.024) was detected. Indeed, females showed higher level of BRUCE expression than male patients. Since specific expression of BRUCE protein was revealed in majority of GC tissues, BRUCE protein may be a useful therapeutic target for cancer therapy. Furthermore, based on the native role of BRUCE protein in inhibition of apoptosis, using this protein in targeted therapy of tumor cells may help to inhibit tumor cells growth and survival leading to rapid elimination of tumor mass.
There is an inevitable association between cell signaling pathways and tumorigenesis. Wnt and not... more There is an inevitable association between cell signaling pathways and tumorigenesis. Wnt and notch pathways play important roles during development and self-renewal. Beside the independent role of such pathways on tumor progression, different cross talks between these pathways through tumorigenesis are emphasized. In this study, we analyzed cross talk between Wnt and NOTCH signaling pathways through assessment of probable correlation between MAML1 and PYGO2 as the main transcription factors of these pathways, respectively in esophageal squamous cell carcinoma (ESCC) patients. Levels of MAML1 and PYGO2 mRNA expression in 48 ESCC patients were compared to the correlated margin normal tissues using real-time polymerase chain reaction (PCR). Eleven out of 48 patients (22.9 %) have shown the concomitant MAML1/PYGO2 over expression in significant correlation with tumor size (p = 0.046) and depth of tumor invasion (p = 0.050). We showed that there is a significant correlation and feedback between these markers during the ESCC progression and metastasis.
Iranian Journal of Basic Medical Sciences, Nov 1, 2014
Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes ... more Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs) are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR). Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line) compared with normal esophageal tissue of ESCC patients. Rate of transfection in KYSE30 was also between 40 to 50%, using the pSilencer-Brg1shRNA (1:1 ratio). Our data indicated that chromatin remodeling machinery is a novel aspect in tumor biology of ESCC, and overexpression of Brg1 as an important member of SWI/SNF might be involved in the migration and invasion of ESCC tumoral cells.
Developmental pathways such as Wnt and Notch are involved in different cellular functions from th... more Developmental pathways such as Wnt and Notch are involved in different cellular functions from the cell cycle regulation to self-renewal. Therefore, aberrations in these pathways may cause tumorigenesis. Msi1 has a critical regulatory role for the Wnt and Notch pathways. In the present study, we have assessed the probable correlation between the Msi1 and MAML1 in esophageal squamous cell carcinoma (ESCC) progression and metastasis. Levels of Msi1 and MAML1 mRNA expression in 51 ESCC patients were compared to the normal tissues using real-time polymerase chain reaction (PCR). Nine out of 51 (17.6 %) cases had Msi1/MAML1 overexpression, and there was a significant correlation between such overexpressed cases and tumor location (p = 0.013). We showed that there is not any direct correlation and feedback between the Msi1 and MAML1 in ESCC patients.
Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes ... more Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs) are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR). Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line) ...
Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, a... more Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21. In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR). Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035). Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC.
Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stabilit... more Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects. Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter. It was observed that, 12 out of 39 cases (23.5%) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4%, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p = 0.028) and location (p = 0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis. The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer.
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Papers by Meysam Moghbeli