scholarly journals MARCH1 Interacts with β-Catenin as a New Oncogene for Gastric Cancer

2021 ◽  
Author(s):  
Nuan Wang ◽  
Lijuan Yang ◽  
Da Yan ◽  
Xingfang Jia ◽  
Juanjuan Dai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Clinical Stage ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Biological Behavior ◽  
Gastric Cancer Cells

Abstract Background:Membrane-associated RING-CH 1 (MARCH1) is an E3 ubiquitin ligase that plays an important role in antigen presentation. The latest research found that MARCH1 can either promote or suppress cancer progression in ovarian, liver, and bladder cancers, but its function in gastric cancer has not been addressed. This study aimed to investigate the role of MARCH1 in gastric cancer.Methods:The Cancer Genome Atlas (TCGA) database was used to evaluate the expression level and biological function of MARCH1 in gastric cancer. We down-regulated and up-regulated the expression level of MARCH1 in gastric cancer cell line AGS by transfecting siRNAs and overexpression plasmids. Then we detected cell proliferation, migration, invasion and apoptosis using CCK-8 assay, transwell chamber assay and flow cytometry respectively. The relationship between MARCH1 and β-catenin was analyzed using western blotting assay. Results:The results showed that the expression of MARCH1 in gastric cancer was elevated and significantly related to clinical stage, tumor grade, and lymph node metastasis. It is worth noting that there was no significant correlation between the increase in MARCH1 expression level and overall survival. In addition, knocking down and upregulating the expression level of MARCH1 significantly affected the proliferation, migration, invasion, and apoptosis of gastric cancer cells. Furthermore, the study found that MARCH1 and β-catenin positively regulated each other, suggesting that MARCH1 may participate in the malignant biological behavior of tumors through the Wnt/β-catenin pathway.Conclusions:In summary, this study shows the function of MARCH1 in the progression of gastric cancer and provides unique insights into the regulatory mechanism of MARCH1 and β-catenin, which indicates that MARCH1 may be a new target molecule for gastric cancer.

scholarly journals miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shihua Wu ◽  
Feng Liu ◽  
Liming Xie ◽  
Yaling Peng ◽  
Xiaoyuan Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.

scholarly journals Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation

2021 ◽  
Author(s):  
Yinggang Hua ◽  
Long Li ◽  
Liangliang Cai ◽  
Guoyan Liu
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Promoter Region ◽  
Methylation Status ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Receptor Activation ◽  
Diffuse Gastric Cancer ◽  
Gastric Cancer Cells

Abstract P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, its DNA methylation status or even the corresponding regulatory mechanism remains unknown. In this study, DNA methylation chip was used to profile the genome-wide DNA methylation level in gastric cancer tissues. Proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with 4 hypermethylated sites (|Δβ value| >0.2) in diffuse gastric cancer and then were validated by bioinformatic analysis in TCGA database. Analysis of MRS2365-treated cells by annexin-V/PI staining and Caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 may have contributed to the reduced expression of P2RY1’s mRNA, which is likely responsible for the “aggressive” nature of the diffuse type gastric cancer.

The Effect of Dihydroartemisinin on the Malignancy and Epithelial-Mesenchymal Transition of Gastric Cancer Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 719-726 ◽  
Author(s):  
Nan Li ◽  
Suyun Zhang ◽  
Qiong Luo ◽  
Fang Yuan ◽  
Rui Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition ◽  
Expression Levels

Objective: This study aimed to observe the effects of dihydroartemisinin (DHA) on the proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT) of the human gastric cancer cell line SGC7901 cultured in vitro. Methods: We applied varying concentrations of DHA to SGC7901 cells. Cell proliferation was measured using the cell counting kit-8 (CCK-8). Flow cytometry, Transwell invasion assay, and cell scratch assay were used to investigate the cells’ apoptosis, invasion, and migration. Western blot was used to assess the expression levels of EMT markers E-cadhein and Vimentin, protein kinases Akt and phosphorylated AKT (p-AKT), and the cell transcription factor Snail. Results: DHA can effectively inhibit the malignant proliferation of gastric cancer cells in a time- and dose-dependent manner. In this study, with longer incubation times and increased drug concentrations, the antiproliferation effect of DHA on SGC7901 cells increased gradually (P<0.05). In addition, with the increase of drug concentration, the expression levels of E-cadhein, an epithelial-mesenchymal transition marker, remarkably increased, whereas the protein expression levels of the mesenchymal markers Vimentin, Akt, p-Akt, and Snail significantly decreased (P<0.05). Conclusion: DHA can effectively inhibit the proliferation, invasion, and metastasis of the gastric cancer cell line SGC7901 and induce cancer cell apoptosis. DHA can also downregulate PI3K/AKT and Snail activities and inhibit the epithelial-mesenchymal transition of gastric cancer cells. The potential anticancer effects of DHA deserve further investigation.

scholarly journals Efficacy of Metformin and Chemotherapeutic Agents on the Inhibition of Colony Formation and Shh/Gli1 Pathway: Metformin/Docetaxel Versus Metformin/5-Fluorouracil

Drug Research ◽  
2020 ◽  
Vol 71 (01) ◽  
pp. 17-25
Author(s):  
Maryam Fatehi-Agdam ◽  
Mohammad Amin Vatankhah ◽  
Reza Panahizadeh ◽  
Farhad Jeddi ◽  
Nowruz Najafzadeh
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Gastric Cancer Cells ◽  
Anticancer Effects ◽  
Chemotherapy Agents

Abstract Background Gastric cancer is a common gastrointestinal cancer characterized by poor prognosis and chemoresistance. Docetaxel and 5-fluorouracil (5-FU) are frequently used for the treatment of gastric cancer. Despite their potent anti-cancer effects, chemoresistance occurs in metastatic gastric cancer. Metformin, a popular anti-diabetic drug, has been proven to have potent anticancer effects on gastrointestinal cancers. Here, we aim to improve this chemotherapy agents’ efficacy by pretreatment with metformin. Methods The AGS gastric cancer cell line were pretreated with three different sub-toxic concentration of metformin and then treated with various concentrations of 5-FU and docetaxel.The anticancer effects of the combination of metformin with the chemotherapy agents were determined using clonogenic assay and DAPi staining. We used real-time PCR to evaluate Gli1, Gli2, and TWIST1 mRNA expression levels in the gastric cancer cells. Also, the expression of the Shh protein was assessed using immunocytochemistry. Results Here, we found that metformin sensitized the gastric cancer cells to chemotherapy. The combination treatments were more effective in reducing the number of cancer colonies compared to 5-FU or docetaxel alone. The combination of metformin with 5-FU or docetaxel significantly reduced the number of cells expressing the Shh protein compared to the 5-FU alone or docetaxel alone. Interestingly, we found that the combination of metformin with docetaxel significantly down-regulated the mRNA levels of Gli1, Gli2, and TWIST1 in the AGS gastric cancer cell line compared to docetaxel alone. Conclusion Overall, our data strongly support an important role for metformin as an enhancer of the efficacy of chemotherapeutic agents against gastric cancer.

scholarly journals Autophagy induced by H. pylori VacA regulated the survival mechanism of the SGC7901 human gastric cancer cell line

2021 ◽  
Author(s):  
Juan Luo ◽  
Luyan Bai ◽  
Jun Tao ◽  
Yu Wen ◽  
Mingke Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Molecular Mechanism ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
H Pylori

Abstract Background Vacuolating cytotoxin (VacA) is an important virulence factor of Helicobacter pylori (H. pylori). It was previously believed that VacA can trigger the cascade of apoptosis on mitochondria to lead to cell apoptosis. Recently, it was found that VacA can induce autophagy. However, the molecular mechanism by which VacA induces autophagy is largely unknown. Objective We aimed to explore the molecular mechanism of autophagy induced by H. pylori in gastric cancer cells and the effect of autophagy on the survival of gastric cancer cells. Methods The autophagy of human gastric cancer cell line SGC7901 was detected by Western blot and RT-PCR in the treatment of VacA protein of H. pylori. The relationship between autophagy and reactive oxygen species (ROS) in the proliferation of gastric cancer cells were studied by gene expression silences (siRNA) and CM-H2DCFDA (DCF) staining. Results The results showed that VacA protein secreted by H. pylori in the supernatant stimulated autophagy in SGC7901 cells. After VacA protein treatment, the mRNA expressions of BECN1, ATG7 and PIK3C3, were up-regulated. ATG7 silencing by siRNA inhibited VacA-induced autophagy. Furthermore, our data demonstrated that VacA protein increased ROS levels. Addition of the antioxidant N-acetyl-l-cysteine (NAC) suppressed the levels of ROS, leading to inhibition of autophagy. Conclusions H. pylori VacA is a key toxin that induces autophagy by increased ROS levels. And our findings demonstrated that VacA significantly inhibited proliferation in SGC7901 cells.

scholarly journals Cisplatin-Resistant Gastric Cancer Cells Promote the Chemoresistance of Cisplatin-Sensitive Cells via Exosomal RPS3 Mediated PI3K-Akt-cofilin-1 Signaling Axis

2020 ◽  
Author(s):  
Mengyao Sun ◽  
Bo Xu ◽  
Qiuxue Wu ◽  
Si Cai ◽  
Wenlian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
In Vitro Assays ◽  
Mechanism Study ◽  
Gastric Cancer Cells ◽  
Receptor Cells

Abstract Background: Cisplatin is an important agent in first-line chemotherapy against gastric cancer (GC). However, consequential drug resistance limits its effectiveness for the treatment of GC. Exosomes which are loaded with proteins, lipids and RNAs, have been proven to transfer malignant phenotype. This study aims to explore the role and mechanism of exosomal RPS3 protein in transmitting a chemoresistance phenotype from cisplatin resistant to cisplatin sensitive gastric cancer cells.Methods: A cisplatin resistant gastric cancer cell line SGC7901R was established by continuously grafting SGC7901S cells into cisplatin-containing culture medium. Exosomes from SGC7901R and SGC7901S were obtained and confirmed through ultracentrifuge and Nano Analyzer. By LC-MS/MS analysis methods, we detected the differentially expressed proteins in SGC7901R cells exosomes and SGC7901S cells exosomes. Western blotting was used to verify the differential expression of exosomal RPS3 between cisplatin resistant and parental cell lines. Subsequently, a series of in vitro assays and a xenograft tumor model were used to observe the functions of exosomal RPS3 protein in GC.Results: SGC7901R cell derived exosomes were readily taken up by cisplatin sensitive SGC7901S cells, thus triggering off a phenotype of chemoresistance in the receptor cells. Subsequently, it was demonstrated that exosomal RPS3 was essential for inducing chemoresistance of receptor cells as shown by the acquisition of this phenotype in SGC7901S cells with enforced expression of RPS3. Further mechanism study demonstrated that cisplatin‑resistant gastric cancer cells-derived exosomal RPS3 enhanced the chemoresistance of cisplatin‑sensitive gastric cancer cells through the PI3K-Akt-cofilin-1 signaling pathway.Conclusion: Cisplatin resistant gastric cancer cells communicate with sensitive cells through the intercellular delivery of exosomal RPS3 and activation of the PI3K-Akt-cofilin-1 signaling pathway. Targeting exosomal RPS3 protein in cisplatin resistant gastric cancer cells may thus be a promising strategy to overcome cisplatin resistance in gastric cancer.

scholarly journals Clinical Significance of MicroRNA-155 Regulated Autophagy and Apoptosis by targeting gene Rictor/Fos in Gastric Cancer Progression

2020 ◽  
Author(s):  
Gang Chen ◽  
Yu Li ◽  
Zhijian Ren ◽  
Yanmei Gu ◽  
Futian Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Progression ◽  
Target Genes ◽  
Clinical Stage ◽  
Expression Level ◽  
Apoptosis Pathway ◽  
Significant Difference ◽  
Cancer Tissues ◽  
Low Expression

Abstract BACKGROUND Microrna-155 plays an important role in the pathogenesis, progression and treatment of various cancers. It is abnormally expressed in gastric cancer, but its expression level, mechanism and significance are controversial in different studies. So we make the study to explore the expression level, significance and mechanism of microRNA-155 on gastric cancer. METHODS Target genes of microRNA-155 in TargetScan and mirDB databases were analyzed by Wayne Mapping, Enrichr database, String database, TIMER database. Forty-three pairs of cancer tissues and adjacent tissues were collected to extract total RNA and protein. Expression of MicroRNA-155, Rictor, Fos, Beclin1, LC3, caspase3 and caspase9 were measured by qRT-PCR and western blot. The relationship between gene expression and clinicopathological factors were analyzed. SPSS 23.0 was used for statistical analysis. RESULTS A total of 700 (miRDB) and 556 (TargetScan) target genes were obtained and 280 genes were in the intersection of Wayne Mapping, 49 of them had a target score of 90 or more. GO and KEGG analysis revealed that they were related to autophagy or apoptosis pathway. Rictor and Fos were selected as research objects. Thirty-two cases showed high microRNA-155 expression (group H) and 11 cases showed low expression (group L). Twelve patients had high Rictor expression and 31 patients had low expression; Thirteen cases had roughly normal Fos expression and 30 cases had low or negative expression; Thirty-three cases had high Beclin1/LC3 expression and 10 cases had low expression; Ten cases had high caspase3/caspase9 expression and 33 cases had low expression. According to the results of immunohistochemistry and western blot, Rictor, Fos, caspase3 and caspase9 were low expressed while Beclin1 and LC3 were high expressed in group H. However, all the six genes had no significant difference in group L. CONCLUSIONS The abnormal expression of microRNA-155 may indicate the occurrence of gastric cancer and its expression level is negatively correlated with clinical stage of cancer. The down-regulated expression of Rictor and Fos, enhancement of autophagy and weakening of apoptosis may be related to the over-expression of microRNA-155. MicroRNA-155 may promote the progression of gastric cancer by promoting autophagy and inhibiting apoptosis.

scholarly journals Transcriptional activation of the human claudin-18 gene promoter through two AP-1 motifs in PMA-stimulated MKN45 gastric cancer cells

2008 ◽  
Vol 294 (1) ◽  
pp. G336-G343 ◽  
Author(s):  
Koichi Yano ◽  
Takashi Imaeda ◽  
Tomoaki Niimi
Keyword(s):  
Gastric Cancer ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Gene Promoter ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Mitogen Activated Protein Kinase ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Mobility Shift

Claudin-18 ( CLDN18), a member of the claudin family of proteins that are structural components of tight junctions, has two alternatively spliced variants, claudin-18a1 and claudin-18a2, which are highly expressed in lung and stomach, respectively. Downregulation of claudin-18a2 is associated with gastric cancers of an intestinal phenotype; however, the mechanisms regulating its expression have not been defined. Here, we found that phorbol 12-myristate 13-acetate (PMA) treatment of MKN45 human gastric cancer cell line increased claudin-18a2 expression. In addition, this study aimed to characterize the human CLDN18a2 promoter. Using reporter gene assays and deletion analysis, we mapped the critical promoter region of the PMA-stimulated claudin-18a2 expression to the −923/−286 region. Electrophoretic mobility shift assays and mutational analyses revealed that two activator protein (AP)-1 binding sites played an important role in the expression of claudin-18a2 in PMA-stimulated MKN45 cells. Protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) inhibitors suppressed the upregulation of claudin-18a2. These results indicate that the PKC/MAPK/AP-1 dependent pathway regulates claudin-18a2 expression in gastric cells.

CD44-overexpressed gastric cancer imaging by near IR using HA-based supramolecular hydrogels.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 34-34
Author(s):  
Jungmin Park
Keyword(s):  
Gastric Cancer ◽  
Optical Imaging ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Gastric Cancer Cells

34 Background: To establish NIR optical probe based on the HA-based supramolecular hydrogels (HASHs) conjugated with Cy5.5 for CD44-overexpressed gastric cancer imaging. Methods: To establish HASHs, Cy5.5 NHS ester was conjugated with polyethyleneimine (PEI, 25k Da) and mixed with hyaluronic acid (HA, 1M Da) by an electric interaction. The optimazed ideal molar ratio of PEI to HA was confirmed by DLS and gel electrophoresis. The CD44-expression level for various gastric cancer cell lInes (MKN1, MKN28, MKN45, MKN72, AGS, and N87 cells) was evaluated by FACS analysis. For establishment of the gastric cancer xenograft model, CD44-overexpressed gastric cancer cells were implanted into the BALB/c nude mouse's proximal thigh region. For in vitro targeting study, the cellular affinity of HASHs for CD44-low expressed gastric cancer cell line and CD44-overexpressed gastric cancer cell line was verified by confocal microscopy and IHC staing. For in vivo NIR imaging, HASHs were injected into established xenograft mouse via tail vein and NIR optical imaging was conducted time-dependently. Results: The colloidal size of HASHs was 1.4 micrometer and their morphology was confirmed by electron microscopy. CD44-expression level of MKN45 cells was 92.53% that was higher than MKN28 cells (2.66%). After the treatment of HASHs, the endocytosis into the cytosol was examined for MKN45 cells, but not observed in MKN28 cells due to the deficiency of CD44. 30 days after the transplantion of MKN45 cells, for in vivo imaging study, the prepared HASHs were intraveneously injected into tumor-bearing mouse model. By NIR optical imaging, the optical intensity at tumor site was enhanced upto 3 hours and the maximum intensity was 350 times larger than normal tissue. Conclusions: HASHs was established using supramolecular HA and Cy5.5-conjugated PEI for the targeted imaging of CD44-overexpressed gastric cancer cells. In vitro and in vivo studies demonstrated that SHAHs can visualize the individualized CD44-overexpressed gastric cancer cells by non-invasive optical imaging.

scholarly journals Upregulation of long noncoding RNA SNHG1 indicates a poor prognosis in patients with gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Expression Levels

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.

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