scholarly journals The LINC00152/miR-138 Axis Facilitates Gastric Cancer Progression by Mediating SIRT2

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jinchun Wang ◽  
Jie Wu ◽  
Lei Wang ◽  
Xuewen Min ◽  
Zhujing Chen
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Tumor Therapy ◽  
Bioinformatic Analysis ◽  
Clinicopathological Characteristics ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Downstream Target ◽  
Reduce Cell Proliferation

Gastric cancer (GC) is the most common gastrointestinal cancer and the main cause of tumor-related death. Exploring markers for early diagnosis and new therapeutic targets is always on the way. In the last 10 years, long noncoding RNAs (lncRNAs) have been widely proved to be involved in the progress of many tumors and are regarded as potential targets for tumor therapy. We found that LINC00152, a newly identified lncRNA, was significantly upregulated in GC tissues and affected clinicopathological characteristics in GC patients. Furthermore, we observed that LINC00152 knockdown can significantly reduce cell proliferation and promote apoptosis in human gastric cancer cells. Further bioinformatic analysis indicated that LINC00152 competitively bound with miR-138 and regulated the expression of miR-138. Moreover, SIRT2 was further proved to be a downstream target of miR-138. Overall, this study elucidates the molecular mechanism of LINC00152 underlying the malignant phenotype of GC cells by mediating miR-138/SIRT2 axis, which provides a new understanding of the role and molecular mechanism of lncRNA in GC and also provides a new way for the treatment of 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 The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a′]diisoquinoline derivatives in human gastric cancer cells

2018 ◽  
Vol 36 (6) ◽  
pp. 970-984 ◽  
Author(s):  
Natalia Pawłowska ◽  
Agnieszka Gornowicz ◽  
Anna Bielawska ◽  
Arkadiusz Surażyński ◽  
Anna Szymanowska ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

2017 ◽  
Vol 41 (3) ◽  
pp. 907-920 ◽  
Author(s):  
Jing Li ◽  
Lujun Chen ◽  
Yuqi Xiong ◽  
Xiao Zheng ◽  
Quanqin Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Over Expression ◽  
Gastric Cancer Cell Lines ◽  
Cancer Tissues

Background/Abstract: PD-L1 has been an important target of cancer immunotherapy. We have showed that in human gastric cancer tissues, over-expression of PD-L1 was significantly associated with cancer progression and patients’ postoperative prognoses. However, as of now, how PD-L1 regulates the biological function of gastric cancer cells still remains elusive. Methods: We constructed the stable PD-L1 knockdown expression gastric cancer cell lines by using RNAi method, and further investigated the changes of biological functions including cell viability, migration, invasion, cell cycle, apoptosis, tumorigenicity in vivo, and the cytotoxic sensitivity to CIK therapy, in contrast to the control cells. Results: In the current study, we demonstrated that the knockdown of PD-L1 expression in human gastric cancer cells could significantly suppress the cell proliferation, migration, invasion, apoptosis, cell cycle, tumorigenicity in vivo and the cytotoxic sensitivity to CIK therapy. Conclusion: Our results indicate that PD-L1 contributes towards transformation and progression of human gastric cancer cells, and its intervention could prove to be an important therapeutic strategy against gastric cancer.

scholarly journals Rev-erbα inhibits proliferation by reducing glycolytic flux and pentose phosphate pathway in human gastric cancer cells

Oncogenesis ◽  
2019 ◽  
Vol 8 (10) ◽  
Author(s):  
Linlin Tao ◽  
Haoyuan Yu ◽  
Rui Liang ◽  
Ru Jia ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Pentose Phosphate Pathway ◽  
Inflammatory Responses ◽  
Pentose Phosphate ◽  
Glycolytic Flux ◽  
Human Gastric Cancer ◽  
Dependent Manner ◽  
Gastric Cancer Cells

Abstract Rev-erbα is a nuclear receptor, which regulates circadian rhythm, inflammatory responses and lipid metabolism. We previously showed Rev-erbα reduction in human gastric cancer, which is associated with TMN stages and poor prognosis. We hypothesized that Rev-erbα modulates proliferation via glycolytic flux and the pentose phosphate pathway (PPP) in gastric cancer. Knockdown of Rev-erbα significantly increased proliferation as well as glycolytic flux and the PPP in human gastric cancer cells. These effects were reduced by a Rev-erbα agonist GSK4112 in a dose-dependent manner. Furthermore, Rev-erbα was recruited on the promoters of PFKFB3 and G6PD genes, thereby inhibiting their gene transcription. GSK4112 treatment reduced PFKFB3 and G6PD gene expression, which was not affected by BMAL1 knockdown. Pharmacological inhibition of glycolysis and the PPP using corresponding PFKFB3 and G6PD inhibitors attenuated Rev-erbα knockdown-induced proliferation in gastric cancer cells. GSK4112 treatment was not able to reduce proliferation in SGC-7901 overexpressing both PFKFB3 and G6PD genes. Both PFKFB3 and G6PD were overexpressed in patients with gastric cancer, and positively correlated with the TMN stages. The PPP and glycolysis were enhanced in gastric cancer tissues of patients with low expression of Rev-erbα compared to the patients with high expression of Rev-erbα. In conclusion, Rev-erbα reduction causes gastric cancer progression by augmenting the PPP and glycolysis.

scholarly journals PolG Inhibits Glycolysis by Suppressing PKM2 Phosphorylation Resulting Reduced Gastric Cancer Proliferation

2020 ◽  
Author(s):  
Mengzhu Lv ◽  
Simeng Zhang ◽  
Yuqing Dong ◽  
Liu Cao ◽  
Shu Guo
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Tumor Formation ◽  
Cell Counting ◽  
Mechanism Analysis ◽  
Gastric Cancer Cells ◽  
The Impact

Abstract Background: Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death. There is a critical need for the development of novel therapies in GC. DNA polymerase gamma (PolG) has been implicated in mitochondrial homeostasis and affects the development of a numerous of cancer types. However, its effects in GC and molecular mechanisms remain to be fully determined. Methods: GSE62254 dataset was used to predict the impact of PolG on prognostic valule in GC patients. Lentivirus-mediated transduction was used to silence PolG expression. Western blot analysis the knockdown effect. Co-immunoprecipitation analysis was performed to explore the potential molecular mechanism. Analysis of the glycolysis process in GC cells was also performed. Cell proliferation was determined using a CCK-8 (Cell Counting Kit-8) proliferation assay. Cell migration was detected using transwell method. Animal experiment was used to measure the In vivo xenograft tumor growth.Results: GC patients with low PolG expression have worse OS and pFS . PolG binds to PKM2 and affects the activation of the Tyr105 site phosphorylation, then interfering with the glycolysis of Gastric cancer cells. In vitro tumor formation experiments in mice also confirmed that PolG knockdown GC has stronger proliferation ability. PolG can suppress GC cells growth in both vivo and vitro.Conclusion: Our study reveals a potential molecular mechanism between PolG and the energy metabolic process of GC tumor cells, suggesting PolG as an independent novel potential therapeutic target for tumor therapy.

scholarly journals Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 axis

2020 ◽  
Author(s):  
Qi Zhou ◽  
Yuan Li ◽  
Lujun Chen ◽  
Xiao Zheng ◽  
Tianwei Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Regulatory Relationship ◽  
Downstream Target ◽  
Rnai Technology

Abstract Backgroud Long non-coding RNAs (lncRNAs) played important roles in various biological processes and human diseases, including cancer. Methods In this study, RNAi technology, RNA-FISH, RNA-pull down assay and cellular function studies were used to demonstrate a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Results Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target gene of miR-375, and established the important role of GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Conclusions Our results revealed a novel mechanism of GRIK1-AS1 as sponge to miR-375that impact gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, open a new strategy to future GRIK1-AS1 based therapeutic development.

NSD1 stimulated survival and migration of gastric cancer cells through WNT10B

2021 ◽  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Cancer Tissues

Background and objective: To assess the expression of Nuclear receptor binding SET domain protein 1 (NSD1) in human gastric cancer tissues and cells and investigate its possible role in gastric cancer. Methods: TCGA database was used to assess the expression levels of NSD1 in human gastric cancer tissues. Immunoblot assays were performed to detect NSD1 expression levels in gastric cancer cell lines. MTT and colony formation assays were conduced to detect its role in the survival of gastric cancer cells. Wound closure and transwell were performed to investigate the effects of NSD1 on the motility of gastric cancer cells. Immunoblot assays were also conducted to confirm its effects on WNT10B/β-catenin pathway. Results: We found the high expression levels of NSD1 in human gastric cancer tissues and cell lines. NSD1 depletion suppressed the survival and motility of gastric cancer cells. Additionally, we revealed NSD1 activated the WNT10B/β-catenin pathway, therefore promoted gastric cancer progression. Conclusion: We revealed the high NSD1 expression in gastric cancer tissues and cells, and thought NSD1 could serve as a promising gastric cancer target.

Investigating chemopotentiation by low-dose fractionated radiation therapy for disseminated intra-abdominal gastric cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 242-242
Author(s):  
France Carrier ◽  
Palak Parekh ◽  
Eduardo Solano-Gonzalez ◽  
Xinrong Ma ◽  
Kayla Tighe ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Radiation Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Low Dose ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Potential Biomarker ◽  
Fractionated Radiation Therapy ◽  
Fractionated Radiation

242 Background: Treatment options are rather limited for gastrointestinal cancer patients whose disease has disseminated into the intra-abdominal cavity. There is currently no modality that has been shown to prolong survival of this patient sub-population. Here, we designed pre-clinical studies to evaluate the potential application of chemopotentiation by Low Dose Fractionated Radiation Therapy (LDFRT) for disseminated gastric cancer and evaluate the role of a likely biomarker, the Dual Oxidase 2 (DUOX2) enzyme. Methods: Nude mice were injected orthotopically with human gastric cancer cells expressing endogenous or lower levels of DUOX2 and randomly assigned to four treatment groups: 1; vehicle alone, 2; chemotherapy consisting of a modified regimen of docetaxel, cisplatin and 5’-fluorouracil (mDCF) for three consecutive days, 3; Low Dose- Whole Abdomen Radiation Therapy (LD-WART) (5 fractions of 15 cGy in three days), 4; mDCF and LD-WART. Blood was harvested at day 14 and 45 and cancer progression was evaluated by fluorescence imaging (Xenogen). Results: The combined regimen was well tolerated in all animals and led to DUOX2 upregulation, increased serum protein oxidation and reduced cancer progression in the DUOX2 positive tumors. Tumors expressing lower DUOX2 levels were more sensitive to chemotherapy but no additional benefit was obtained with LD-WART. The potential clinical significance of these findings is exemplified by a tumor microarray demonstrating that only about 46% of human gastric tumors expressed DUOX2. The molecular mechanisms underlying DUOX2 effects in response to the combined regimen include NF-kB upregulation and VEGF down regulation. Moreover, the combined regimen of mDCF and LDFRT was also effective on a Cancer Stem Cell (CSC)-Like subpopulation of mouse gastric cancer cells. Conclusions: Taken together these data suggest that DUOX2 could be used as a potential biomarker for patient stratification for chemopotentiation by LD-WART for positive tumors while chemotherapy alone would be more effective for DUOX2 negative tumors. The absence of added toxicity suggests that these cycles could be repeated.

scholarly journals Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Zhou ◽  
Yuan Li ◽  
Lujun Chen ◽  
Xiao Zheng ◽  
Tianwei Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Target Genes ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Gastric Cancer Cells ◽  
Regulatory Relationship ◽  
Downstream Target

Long non-coding RNAs (lncRNAs) play important roles in various biological processes and human diseases, including cancer. In this study, we demonstrated a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration, and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target genes of miR-375, and established the important role of the GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Taken together, our results revealed a novel mechanism of GRIK1-AS1 as a sponge to miR-375 that impacts gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, opens a new strategy to future GRIK1-AS1 based therapeutic development.

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