scholarly journals Tenascin-c Knockdown Suppresses Vasculogenic Mimicry of Gastric Cancer by Inhibiting ERK- Triggered EMT

2021 ◽  
Author(s):  
Xing Kang ◽  
en xu ◽  
Xingzhou wang ◽  
Lulu Qian ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Vasculogenic Mimicry ◽  
Gastric Cancer Cells ◽  
Tenascin C ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract BackgroundGastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. Tenascin-c (TNC) plays a pivotal role in VM. Thus, we explored the role of TNC in VM formation in gastric cancer.MethodsGastric cancer tissues and corresponding adjacent tissues were collected from gastric cancer patients after surgery. We used western blot and immunohistochemistry to examine the expression of TNC in tissues and used siRNA and lentivirus to knockdown the TNC expression in gastric cancer cell lines. Then three-dimensional culturing, CCK-8, Edu assay, flow cytometry, trasnwell and pseudopodia formation assay were used to evaluate the function of TNC in gastric cancer cells and bioinformatic prediction was used to explore the mechanism underlying TNC modulating the VM in gastric cancer. Xenograft and peritoneal dissemination model were used to further explore the role of TNC in vivo.ResultsIn this study, we demonstrated that TNC was highly expressed in gastric cancer tissues and correlated with poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. What’s more, rescue experiments showed that activation of p-ERK could reverse the suppressive role of TNC knockdown in gastric cancer cells.ConclusionsTNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease anti-angiogenic therapeutic resistance.

EDD1 predicts prognosis and regulates gastric cancer growth in vitro and in vivo via miR-22

2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Min Yang ◽  
Nan Jiang ◽  
Qi-wei Cao ◽  
Qing Sun
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Patient Survival ◽  
Underlying Mechanism ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Abstract Gastric cancer is the most common digestive malignant tumor worldwild. EDD1 was reported to be frequently amplified in several tumors and played an important role in the tumorigenesis process. However, the biological role and potential mechanism of EDD1 in gastric cancer remains poorly understood. In this study, we are aim to investigate the effect of EDD1 on gastric cancer progression and to explore the underlying mechanism. The results showed the significant up-regulation of EDD1 in -gastric cancer cell tissues and lines. The expression level of EDD1 was also positively associated with advanced clinical stages and predicted poor overall patient survival and poor disease-free patient survival. Besides, EDD1 knockdown markedly inhibited cell viability, colony formation, and suppressed tumor growth. Opposite results were obtained in gastric cancer cells with EDD1 overexpression. EDD1 knockdown was also found to induce gastric cancer cells apoptosis. Further investigation indicated that the oncogenic role of EDD1 in regulating gastric cancer cells growth and apoptosis was related to its PABC domain and directly through targeting miR-22, which was significantly down-regulated in gastric cancer tissues. Totally, our study suggests that EDD1 plays an oncogenic role in gastric cancer and may be a potential therapeutic target for gastric cancer.

Regulation of miR-596 on the Apoptosis of Gastric Cancer Cells through Its Targeting Inhibition of BCL-2

2020 ◽  
Author(s):  
Jianmiao WANG ◽  
Jing YANG ◽  
Ji QIU ◽  
Taoyan SONG
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Gastric Cancer Patients ◽  
Cancer Tissues ◽  
The Relationship

Background: We aimed to investigate the relationship between miR-596, BCL-2, and apoptosis of gastric cancer cells, and to explore the mechanism of miR-596 in gastric cancer. Besides, this study aimed to find the target of miR-596 and explore the mechanism of action of miR-596 in gastric cancer. Methods: Eighteen samples of gastric cancer tissues and 18 samples of corresponding tumor-adjacent tissues were collected from 18 gastric cancer patients (aged from 40 to 55 yr) admitted to Zhuji People's Hospital, Zhuji, China from March 2017 to May 2018. The expression levels of miR-596 and BCL-2 were detected to verify the regulation of miR-596 on the apoptosis and proliferation of gastric cancer cell lines MKN-45 and HGC-27 and its effect on BCL-2 expression. Results: The expression level of miR-596 was notably lower in gastric cancer tissues than in adjacent tissues, and BCL-2 level was notably higher in gastric cancer tissues than in adjacent tissues. After the up-regulation of miR-596 expression, the proliferation of MKN-45 and HGC-27 cells was significantly decreased, the level of apoptosis was significantly increased (P<0.05), and the expression of BCL-2 was decreased. The dual-luciferase report showed that miR-596 had a targeting inhibition of BCL-2. Gastric cancer cells with up-regulated miR596 and BCL-2 had significantly higher proliferation and lower apoptosis than cells with up-regulated miR-596. Conclusions: miR-596 can inhibit the proliferation of gastric cancer cells and promote the apoptosis through its targeting inhibition of BCL-2 expression.

scholarly journals SOX13 Dependent PAX8 Expression Promotes the Proliferation of Gastric Carcinoma Cells

2019 ◽  
Author(s):  
Liang-Yu Bie ◽  
Dan Li ◽  
Yan Wei ◽  
Ning Li ◽  
Xiao-Bing Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cyclin B1 ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Pax8 Expression ◽  
Mgc803 Cell ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract PAX8 is identified as a regulator in the pathogenesis of human tumors and an indicator of the prognosis for patients. However, the role of PAX8 on proliferation in gastric cancer have not been studied. This study was aimed to explore the expression pattern of PAX8 in gastric cancer, and investigate the effect of PAX8 on the proliferation of gastric cancer cells. PAX8 and SOX13 were identified to be synchronously upregulated in primary gastric cancer in human gastric cancer tissues and the gastric cancer datasets of TCGA, and gastric cancer patients of combined high PAX8 and SOX13 expression showed poor prognosis. Furthermore, SOX13 can mediate PAX8 and its targeted genes, Aurora B and Cyclin B1, expression in AGS and MGC803 cell lines. Flow cytometry and EdU incorporation assays showed that silencing PAX8 can block the cell cycle of gastric cancer cell in G1 phase and SOX13 expression can rescue the arrested proliferative process induced by PAX8 silenced in CCK8 and colony formation assays. Thus, combined SOX13 and PAX8 expression regulate the proliferation of gastric cancer cells, and both SOX13 and PAX8 play an oncogene function in gastric cancer.

scholarly journals Knockdown of Kremen2 Inhibits Tumor Growth and Migration in Gastric Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Beibei Chen ◽  
Sai-Qi Wang ◽  
Jinxi Huang ◽  
Weifeng Xu ◽  
Huifang Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Gastric Cancer Cells ◽  
And Migration ◽  
Induced Apoptosis ◽  
Gastric Cancer Patients

Kremen2 (Krm2) plays an important role in embryonic development, bone formation, and tumorigenesis as a crucial regulator of classical Wnt/β-catenin signaling pathway. However, the role of Krm2 in gastric cancer is not clear. The aim of this study was to explore the regulatory role of Krm2 in the tumorigenesis and metastasis of gastric cancer. It was demonstrated that, compared to para-cancerous tissues, Krm2 was significantly up-regulated in gastric cancer tissues and was positively correlated with the pathological grade of gastric cancer patients. Given that Krm2 is abundantly expressed in most tested gastric cancer cell lines, Krm2 knockdown cell models were established and further used to construct mice xenograft model. After knocking down Krm2, both the cell survival in vitro and tumorigenesis in vivo of gastric cancer cells were inhibited. At the same time, knockdown of Krm2 induced apoptosis, cell cycle arrest at G2/M phase and repression of migration in gastric cancer cells in vitro. Mechanistically, we found that knockdown of Krm2 suppressed PI3K/Akt pathway. Therefore, we revealed the novel role and the molecular mechanism of Krm2 in promoting the tumorigenesis and metastasis in gastric cancer. Krm2 can be a potent candidate for designing of targeted therapy.

scholarly journals The circBVES Acts as a Sponge of miR-145-5p to Promote Gastric Cancer Glycolysis and Progression Through Regulating HMGB3 Expression

2020 ◽  
Author(s):  
Lu Jin ◽  
Zhiwei He ◽  
Changhao Zhu ◽  
Guoliang Xiao ◽  
Xianjin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Quantitative Polymerase Chain Reaction ◽  
Gastric Cancer Cells ◽  
Repressive Effect ◽  
Cancer Tissues

Abstract Background: CircRNA is a new type of non-coding RNA that has attracted much attention for involvement in the development and progression of various human diseases, especially cancer. The most reported role of circRNA in many tumors is ‘MiRNA sponge’. We aimed to investigate the role of circBVES in the proliferation and glycolysis of gastric cancer cells and its molecular mechanisms.Methods: In this study, higher CircBVES expression in gastric cancer tissues was detected by RNA sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of CircBVES in gastric cancer tissues, and the relationship between the expression of CircBVES and prognosis was further analyzed. Then, the effects of CircBVES on the growth and glycolysis of gastric cancer cells were investigated through in vitro and in vivo functional experiments. The interaction between CircBVES and miR-145-5p was detected by bioinformatics analysis, luciferase activity assay and RNA immunoprecipitation.Results: We found that the expression of CircBVES in gastric cancer tissues was evidently up-regulated, and its level was closely correlated with the prognosis of patients with gastric cancer. Inhibition of CircBVES decreased cell proliferation and glycolysis in vitro. Low expression of CircBVES inhibited tumor growth in vivo. Mechanism analysis showed that CircBVES may serve as a competitive endogenous RNA of miR-145-5p to reduce the expression of miR-145-5p in gastric cancer cells, and relieve the repressive effect of miR-145-5p on target genes HMGB3 and cycle-related proteins CCNE1 and CDK2.Conclusions: Our results suggest that CircAGFG1 may promote the progress of gastric cancer through the CircBVES / miR-145-5p / HMGB3 axis, providing a new target for the treatment of gastric cancer cells.

scholarly journals DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3463
Author(s):  
Sheng-Fan Wang ◽  
Kuo-Hung Huang ◽  
Wei-Chuan Tseng ◽  
Jeng-Fan Lo ◽  
Anna Fen-Yau Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion ◽  
Gastric Cancers ◽  
Gastric Cancer Patients

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. Methods: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. Results: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown–induced cell migration and invasion of gastric cancer cells. Conclusions: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.

scholarly journals Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xing Kang ◽  
En Xu ◽  
Xingzhou Wang ◽  
Lulu Qian ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Vasculogenic Mimicry ◽  
Gastric Cancer Tissue ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Tenascin C ◽  
Gastric Cancer Patients

AbstractGastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

scholarly journals E2F1 Maintains Gastric Cancer Stemness Properties by Regulating Stemness-Associated Genes

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yan Fu ◽  
Cheng’en Hu ◽  
Peizhun Du ◽  
Guangjian Huang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Close Association ◽  
Gastric Cancer Cells ◽  
Cancer Stemness ◽  
Gastric Cancer Patients ◽  
Cancer Tissues ◽  
E2f1 Expression

Purpose. To determine the regulatory role of E2F1 in maintaining gastric cancer stemness properties and the clinical significance of E2F1 in gastric cancer. Materials and Methods. We conducted a tumor spheroid formation assay to enrich gastric cancer stem-like cells. The protein and mRNA expression levels of genes were measured using Western Blot and qRT-PCR. Lentivirus-mediated overexpression and downregulation of E2F1 were performed to evaluate the effect of E2F1 on the stemness properties of gastric cancer cells. The effect of E2F1 on gastric cancer cell sensitivity of 5-Fu was evaluated using cell viability assay and TdT-mediated dUTP Nick-End Labeling staining. We also analyzed the association between E2F1 expression and clinical characteristics in gastric cancer patients. The KM plotter database was used to analyze the relationship between E2F1 and overall survival in GC patients. Results. We found that E2F1 expression was significantly higher in gastric cancer tissues than in the paired adjacent normal tissues ( p < 0.05 ) and was positively correlated with tumor size ( p < 0.05 ), T stage ( p < 0.05 ), and differentiation degree ( p < 0.05 ). KM plotter database demonstrated a close association between higher E2F1 expression level and worse overall survival of gastric cancer patients ( p < 0.05 ). In vitro assay illustrated that E2F1 could regulate the expression of stemness-associated genes, such as BMI1, OCT4, Nanog, and CD44, and maintain the tumor spheroid formation ability of gastric cancer cells. E2F1 enhanced 5-Fu resistance in gastric cancer cells, and the E2F1 expression level was correlated with the prognosis of gastric cancer patients receiving 5-Fu therapy. The expression levels of stemness-associated genes were also significantly higher in gastric cancer tissues than the paired adjacent normal tissues ( p < 0.05 ). A positive correlation was observed between E2F1 and BMI1 (r = 0.422, p < 0.05 ), CD44 (r = 0.634, p < 0.05 ), OCT4 (r = 0.456, p < 0.05 ), and Nanog (r = 0.337, p < 0.05 ) in gastric cancer tissues. The co-overexpression of E2F1 and stemness-associated genes was associated with worse overall survival. Conclusion. E2F1 plays a significant role in gastric cancer progression by maintaining gastric cancer stemness properties through the regulation of stemness-associated genes. The close association between E2F1 and poor prognosis of patients suggests that E2F1 could serve as a prognostic biomarker and a therapeutic target in gastric cancer patients.

LncRNA CRYM-AS1 Inhibits Gastric Cancer Progression via Epigenetically Regulating CRYM

2021 ◽  
Author(s):  
Peipei Zhang ◽  
Changyu Chen ◽  
Jiajia Zhang ◽  
Xin Yu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Aerobic Glycolysis ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Immunoprecipitation Assay ◽  
Gastric Cancer Patients

Abstract Objective: To study the role of long non-coding RNA (lncRNA) CRYM-AS1 in human gastric cancer. Methods: Expression levels of CRYM-AS1 in cell lines and clinical tissues were examined by RT-qPCR. The association between CRYM-AS1 levels and clinicopathological parameters / survival rates of gastric cancer patients was analyzed.Cell functional experiments including MTT assay, glucose consumption / lactate production / ATP production detection were performed to examine the role of CRYM-AS1 in cell aerobic glycolysis and cell proliferation of gastric cancer cells. Subcellular fractionation location detection, western blot, RIP (RNA binding protein immunoprecipitation) assay, CHIP (Chromatin immunoprecipitation) assay and BSP (Bisulfite sequencing PCR) assay were carried out to explore the molecular mechanism of CRYM-AS1 in gastric cancer cells.Results: CRYM-AS1 was low expressed in gastric cancer cells and tissues compared with normal gastric cells and tissues respectively. CRYM-AS1 was negatively correlated with TNM staging, tumor size and overall survival (OS) rate in gastric cancer patients. CRYM-AS1 inhibited gastric cancer cell aerobic glycolysis and cell proliferation. CRYM-AS1 directly bound to EZH2 and mediated the CRYM promoter methylation and consequently negatively regulated the expression of CRYM. Forced expression of CRYM rescued the decreased aerobic glycolysis and cell proliferation induced by CRYM-AS1 in gastric cancer cells.Conclusion: CRYM-AS1 was an important biomarker and could be used for human gastric cancer treatment.

scholarly journals The Association of EBV and Gastric Cancer

2021 ◽  
Author(s):  
Xuming Wang ◽  
Tian Liu ◽  
Lijuan Yu ◽  
Wenfa Mo ◽  
Longkuan Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Caspase 3 ◽  
Gastric Cancer Cells ◽  
Gastric Mucosal Cells ◽  
Expression Levels ◽  
Mucosal Cells ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract The present study aimed to investigate the clinicopathological features of EBV positive and EBV negative gastric cancer patients and the expression levels of proliferative, apoptotic and cell signaling proteins in tissues samples from these patients. The biological role of EBV infection was assessed in gastric cancer. Results: EBV was localized in the nuclei of gastric cancer cells (positive rate 6.86%). The infection rate of EBV in normal gastric mucosal cells, which were adjacent to cancer tissues, was 0. The difference noted was significant (P = 0. 023). The expression levels of caspase-3 (P = 0.0423), FASL (P = 0.00297) and cyclin D1 (P = 0.0345) proteins were significantly different in EBV positive and negative gastric cancer tissues. When the parameters gender, age, Lauren classification, histological grade, early and advanced tumor stage, vascular and nerve invasion, TNM grade and survival status were compared, the maximum tumor diameter, number of lymph node metastasis, caspase-8, Ki67 and P53 protein expression did not reveal significant differences. Bcl-2 protein expression was positive in only one gastric cancer cell sample and negative in the other gastric cancer cell samples as well as in the corresponding normal gastric mucosal epithelial cells. However, significant differences were noted with regard to the positive expression of Bcl-2 in the immune cells of gastric cancer and adjacent tissues (P = 1.17749E-39). The expression levels of Bcl-2 in the immune cells of EBV positive and EBV negative gastric cancer tissues were not significantly different. The expression levels of caspase-8, caspase-3, FASL, Ki67, cyclin D1 and P53 proteins in gastric cancer cells were significantly different compared to those of normal gastric mucosal cells derived from adjacent tissues (P < 0.05). These findings were noted in both EBV positive and/or EBV negative gastric cancer cases (P < 0.05). The survival time of the patients with EBV positive gastric cancer was higher than that of the patients with EBV negative gastric cancer, whereas the differences were not significantly different. The aforementioned results suggested that the EBV virus may directly infect cancerous cells but not normal gastric mucosal cells. With the exception of caspase-3, the expression levels of the proteins FASL and cyclin D1 were closely associated with EBV-positive gastric cancer. EBV did not have a specific effect on the expression of the signaling molecules associated with proliferation and apoptosis of gastric cancer cells. Its effect on gastric cancer cells may be associated with other factors and requires further discussion. No significant differences were noted in the clinicopathological features of EBV positive compared to those of EBV negative gastric cancer patients. However, the prognosis of EBV positive gastric cancer patients was better than that of EBV negative gastric cancer patients. The mechanism of action associated with these processes requires further verification.

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