scholarly journals Hyperglycemia promotes Snail-induced epithelial–mesenchymal transition of gastric cancer via activating ENO1 expression

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Xu ◽  
Bang Chen ◽  
Shaopu Zhu ◽  
Jiawei Zhang ◽  
Xiaobo He ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Gastrointestinal Malignancies ◽  
Mesenchymal Transition

Abstract Background Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear. Method Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion. Results Among the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC. Conclusions Our results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.

Celastrus Orbiculatus Extract Inhibits the Epithelial-mesenchymal Transition Process by Transforming Growth Factor-β Signaling Pathway in Gastric Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Haibo Wang ◽  
Zewen Chu ◽  
Shiya Ou ◽  
Tengyang Ni ◽  
Xiaojun Dai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration

Background: Gastric cancer is the fifth most common tumor and has the third-highest mortality rate among various malignant tumors, and the survival rate of patients is low. Celastrus orbiculatus extract (COE) has been shown to inhibit the activity of a variety of tumors. In this study, we examined the inhibition of the epithelial-mesenchymal transition (EMT) process in gastric cancer cells by COE through the transforming growth factor-β(TGF-β) signaling pathway. Methods: COE was first diluted to various concentrations and then used to treat SGC-7901, BGC-823, MGC-803, and AGS cells. Cell proliferation was assessed by an MTT (thiazole blue) assay. Transwell assays were used to assess cell invasion and migration. The high-content imaging technology was used to further observe the effects of the drug on cell invasion and migration. Western blotting was used to assess the effects of the drug on the expression of EMT and Smad2/3 signaling pathway-related proteins. Results: We found that COE inhibited the migration and invasion of AGS gastric cancer cells in a dose-dependent manner. Consequently, COE decreased the expression of EMT-related proteins and proteins related to the Smad2/3 signaling pathway in gastric cancer cells, inhibiting the migration and invasion of gastric cancer cells, and this effect occurred through the TGF-β signaling pathway. Summary: We investigated that COE could inhibit the proliferation of gastric cancer cells and inhibit invasion and metastasis by inhibiting the EMT process at the molecular level and its effect on the TGF-β signaling pathway.

scholarly journals CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haoqi Zhao ◽  
Lan Wang ◽  
Shufang Wang ◽  
Xihua Chen ◽  
Min Liang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Signaling Pathway ◽  
Cervical Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Mesenchymal Transition ◽  
Gsk 3Β ◽  
Related Proteins

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

scholarly journals A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wanting Song ◽  
Yi Bai ◽  
Jialin Zhu ◽  
Fanxin Zeng ◽  
Chunmeng Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Critical Function ◽  
Mesenchymal Transition ◽  
Patient Prognosis

Abstract Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

scholarly journals GPD1L Suppresses Colon Adenocarcinoma Via Repressing TGFβ1/EMT

2021 ◽  
Author(s):  
Yunqi Li ◽  
Minghao Liu ◽  
zhu xiang ◽  
Xuhui Yang ◽  
Hui Liu
Keyword(s):  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Colon Adenocarcinoma ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Human Beings ◽  
Mesenchymal Transition ◽  
Adenocarcinoma Cells ◽  
Colon Adenocarcinoma Cells

Abstract Colon adenocarcinoma is one of the most prevalent malignant tumors in human beings. Hence, the identification of valuable biomarkers and therapeutic targets is vital for improved treatment and patient outcomes. The role of glycerol-3-phosphate dehydrogenase 1-like (GPD1L) in several tumors has been achieved in recent years. However, the underlying mechanisms of GPD1L in colon adenocarcinoma remain elusive. In this study, we identified that GPD1L was associated with better prognosis in colon adenocarcinoma patients using gene expression omnibus (GEO) and the cancer genome atlas (TCGA) database. In addition, knockdown of GPD1L promoted the proliferation, migration and invasion and reversed by re-expression GPD1L in colon adenocarcinoma cells in vitro. According to gene set enrichment analysis (GSEA), GPD1L is closely correlated with transforming growth factor-β (TGFβ) signaling pathway in colon adenocarcinoma. Moreover, GPD1L downregulates epithelial mesenchymal transition (EMT) marker proteins via TGFβ1 due to Western blot analysis. These findings demonstrate that GPD1L inhibits the growth of colon adenocarcinoma cells by inhibiting EMT induced by TGFβ1. GPD1L may be a promising molecular target for the treatment of colon adenocarcinoma patients.

scholarly journals PADI1 contributes to epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma through activating ERK1/2-p38 signaling pathway

2021 ◽  
Author(s):  
Tengfei Ji ◽  
Keqiang Ma ◽  
Liang Chen ◽  
Tiansheng Cao
Keyword(s):  
Cell Migration ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Survival Prognosis ◽  
Mesenchymal Transition

Abstract Background Peptidylarginine deiminase 1 (PADI1) may be relative with the progression of epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PAAD). We aim to explore the role of PADI1 in PAAD. Methods The expression pattern of PADI1 in PAAD tissues and normal tissues was analyzed using The Cancer Genome Atlas (TCGA) dataset. PADI1 was knocked down in CFPAN-1 and HPAC cells, while overexpressed in PANC-1 and Bxpc-3 cells by RNA interference. Wound healing assay was performed to analyze relative cell migration distance. Cell migration and invasion were assessed by Transwell assay. Related protein expression levels were measured by western blot and immunofluorescence. Results Bioinformatics analysis showed that PADI1 was overexpressed in PAAD tissues and associated with worse survival prognosis. Knockdown of PADI1 suppressed the cell migration, invasion and activated ERK1/2-p38 signaling pathway in CFPAN-1 and HPAC cells. Overexpression of PADI1 obtained the opposite results in PANC-1 and Bxpc-3 cells. Moreover, treatment with MEK1/2 inhibitor significantly recovered the effects of PADI1 knockdown on cell migration, invasion, EMT process and p-ERK1/2 and p38 expression in CFPAN-1 and HPAC cells. Conclusions Our data suggested that PADI1 may function as an oncogene in regulating metastasis in vitro in PAAD.

scholarly journals Oncolytic Adenovirus CD55-Smad4 Suppresses Cell Proliferation, Metastasis, and Tumor Stemness in Colorectal Cancer by Regulating Wnt/β-Catenin Signaling Pathway

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 593
Author(s):  
Boduan Xiao ◽  
Leilei Zhang ◽  
Huihui Liu ◽  
Huiling Fang ◽  
Chunming Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Oncolytic Adenovirus ◽  
Migration And Invasion ◽  
Cell Viability Assay ◽  
Mesenchymal Transition ◽  
Incidence And Mortality

During the past few decades, colorectal cancer (CRC) incidence and mortality have significantly increased, and CRC has become the leading cause of cancer-related death worldwide. Thus, exploring novel effective therapies for CRC is imperative. In this study, we investigated the effect of oncolytic adenovirus CD55-Smad4 on CRC cell growth. Cell viability assay, animal experiments, flow cytometric analysis, cell migration, and invasion assays, and Western blotting were used to detect the proliferation, apoptosis, migration, and invasion of CRC cells. The oncolytic adenovirus CD55-Smad4 was successfully constructed and effectively suppressed CRC cell proliferation in vivo and in vitro. Notably, CD55-Smad4 activated the caspase signaling pathway, inducing the apoptosis of CRC cells. Additionally, the generated oncolytic adenovirus significantly suppressed migration and invasion of CRC cells by overexpressing Smad4 and inhibiting Wnt/β-catenin/epithelial-mesenchymal transition (EMT) signaling pathway. Moreover, CRC cells treated with CD55-Smad4 formed less and smaller spheroid colonies in serum-free culture than cells in control groups, suggesting that CD55-Smad4 suppressed the stemness of CRC cells by inhibiting the Wnt/β-catenin pathway. Together, the results of this study provide valuable information for the development of a novel strategy for cancer-targeting gene-virotherapy and provide a deeper understanding of the critical significance of Smad4 in gene therapy of CRC.

scholarly journals The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

2020 ◽  
Vol 43 (6) ◽  
pp. 1017-1033 ◽  
Author(s):  
Yizhi Xiao ◽  
Side Liu ◽  
Jiaying Li ◽  
Weiyu Dai ◽  
Weimei Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Abstract Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.

scholarly journals microRNA-33a prevents epithelial-mesenchymal transition, invasion, and metastasis of gastric cancer cells through the Snail/Slug pathway

2019 ◽  
Vol 317 (2) ◽  
pp. G147-G160 ◽  
Author(s):  
Di-Di Chen ◽  
Jiang-Ting Cheng ◽  
Arvine Chandoo ◽  
Xiang-Wei Sun ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Node Metastasis

Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a) might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. First, GC tissues and adjacent normal tissues were collected. miR-33a upregulation or SNAI2 depletion on GC cells were introduced to assess the detailed regulatory mechanism of them. We assessed the expression of miR-33a, SNAI2, Snail/Slug signaling pathway-related genes, and EMT-related markers in GC tissues and cells. miR-33a distribution in GC tissues and adjacent normal tissues was measured. Cell proliferation, migration and invasion, and cell cycle distribution were assessed. In nude mice, GC tumor growth and lymph node metastasis were observed. Furthermore, the predicative value of miR-33a in the prognosis of GC patients was evaluated. The obtained results indicated that lowly expressed miR-33a, highly expressed SNAI2, activated Snail/Slug, and increased EMT were identified in GC tissues. miR-33a was located mainly in the cytoplasm. miR-33a targeted and negatively regulated SNAI2. MKN-45 and MKN-28 cell lines were selected for in vitro experiments. Upregulated miR-33a expression or siRNA-mediated silencing of SNAI2 suppressed the activation of Snail/Slug, whereby GC cell proliferation, invasion and migration, EMT, tumor growth, and lymph node metastasis were inhibited. High expression of miR-33a was a protective factor influencing the prognosis of GC. This study suggests that miR-33a inhibited EMT, invasion, and metastasis of GC through the Snail/Slug signaling pathway by modulating SNAI2 expression. NEW & NOTEWORTHY miR-33a targets and inhibits the expression of SNAI2, overexpression of SNAI2 activates the Snail/Slug signaling pathway, the Snail/Slug signaling pathway promotes GC cell proliferation, invasion, and metastasis, and overexpression of miR-33a inhibits cell proliferation, invasion, and metastasis. This study provides a new therapeutic target for the treatment of GC.

scholarly journals Involvement of Wnt/β-catenin pathway in the inhibition of invasion and epithelial-mesenchymal transition in ovarian cancer cells

2020 ◽  
Vol 19 (7) ◽  
pp. 1365-1370
Author(s):  
Belikiz Ekem ◽  
Wei Gong ◽  
Lu Han ◽  
Xinmei Wang ◽  
Na Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Expression Levels

Purpose: To investigate the effects of zerumbone on cell invasion, epithelial-mesenchymal transition (EMT) and the potential signaling pathway involved in ovarian cancer cells.Methods: Caov-3 cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay. Wound healing assay was used to determine Caov-3 cell migration while cell invasion was evaluated using Transwell assay. Protein expression was determinedby western blot.Results: Cell viability was reduced by 5, 10, 20, and 50 μM zerumbone (p < 0.05) in a concentrationdependent manner while cell migration and invasion were inhibited by 10 and 20 μM zerumbone (p < 0.05). Protein expression levels of E-cadherin and cytoplasm β-catenin were upregulated by zerumbone (p < 0.05) in a concentration-dependent manner. On the other hand, protein expression levels of Ncadherin, vimentin, ZEB1, nuclear β-catenin, and c-Myc were suppressed by zerumbone (p < 0.05) also in a concentration-dependent manner.Conclusion: The results demonstrate that zerumbone inhibits cell proliferation, migration and invasion, but represses the EMT process via inactivation of Wnt/β-catenin signaling pathway. Keywords: Zerumbone, Ovarian cancer, Wnt/β-catenin pathway, Epithelial-mesenchymal transition

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