scholarly journals Effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of gastric cancer cells

2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Negative Control ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Ags Cells

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.

scholarly journals IFT80 Improves Invasion Ability in Gastric Cancer Cell Line via ift80/p75NGFR/MMP9 Signaling

2018 ◽  
Vol 19 (11) ◽  
pp. 3616 ◽  
Author(s):  
Rui Wang ◽  
Xiaoyan Deng ◽  
Chengfu Yuan ◽  
Hongmei Xin ◽  
Geli Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Reverse Transcription ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Quantitative Reverse Transcription Pcr ◽  
Reverse Transcription Pcr ◽  
Gastric Cancer Cell Lines

The assembly and maintenance of cilia depend on intraflagellar transport (IFT) proteins, which play an important role in development and homeostasis. IFT80 is a newly defined IFT protein and partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III, both characterized by abnormal skeletal development. However, the role and mechanism of IFT80 in the invasion of gastric cancer is unknown. We established SGC-7901 and MKN-45 gastric cancer cell lines that stably overexpressed IFT80, as verified by quantitative reverse transcription-PCR, Western blot, and immunofluorescence. Matrix metalloproteinase-9 (MMP9) plays an important role in tumor invasion, and its expression was assessed by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence. The invasion ability of IFT80 on SGC-7901 and MKN-45 cells was examined by the Matrigel invasion assay. The relationship between p75NGFR, and the p75NGFR antagonists, PD90780 and IFT80, were detected by quantitative reverse transcription-PCR and Western blotting. We first detected an IFT80 expression pattern, and found that IFT80 was highly expressed in gastric cancer clinical samples. Overexpression of IFT80 in the gastric cancer cell lines, SGC-7901 and MKN-45, led to lengthening cilia. Additionally, overexpression of IFT80 significantly improved proliferation and invasion, but inhibited apoptosis, in gastric cancer cells. We further found that overexpression of IFT80 increased p75NGFR and MMP9 mRNA and protein expression. Treatment with the p75NGFR antagonist PD90780 inhibited the increased invasion ability resulting from overexpression of IFT80 in SGC-7901 and MKN-45 gastric cancer cells. Thus, these results suggest that IFT80 plays an important role in invasion of gastric cancer through regulating the ift80/p75NGFR/MMP9 signal pathways.

scholarly journals Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition

2018 ◽  
Vol 48 (6) ◽  
pp. 2231-2246 ◽  
Author(s):  
Kuan-Fu Liao ◽  
Tsung-Lang Chiu ◽  
Sung-Ying Huang ◽  
Teng-Fu Hsieh ◽  
Shu-Fang Chang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Angelica Sinensis ◽  
Rna Seq ◽  
Gastric Cancer Cells ◽  
Mtor Inhibition

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

miR-3613 Regulates Gastric Cancer Cells Proliferation, Invasion, Migration and Apoptosis by Targeting Suppressor of Cytokine Signaling 4

2019 ◽  
Vol 9 (12) ◽  
pp. 1699-1705
Author(s):  
Yuming Luo ◽  
Wei Cao
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Western Blot ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
And Migration

The present study aimed to investigate the effect of miR-3613 on the biological functions of gastric cancer cell lines. The expression of miR-3613 and SOCS4 in gastric cancer cells were detected by RT-qPCR and western blot. The target genes of miR-3613 were verified with the luciferase reporter system and western blot. The SOCS4 overexpression plasmid was constructed and transfected into gastric cancer cells. To further investigate the function of miR-3613, shRNA targeting miR-3613 and SOCS4 overexpression were transfected into SGC-7901. The growth of cells was detected by CCK-8, then the cell invasion and migration ability were detected by wound healing and transwell. Furthermore, the level of cell cycle was detected by flow cytometry. The expression of cell proliferation, cyclin and migration-related proteins were detected by western blot. The results revealed that the expression of miR-3613 is significantly increased in gastric cancer cells. SOCS4 is one of the target genes of miR-3613. Additionally, interference with miR-3613 promotes cell cycle arrest in gastric cancer cells and reversed the inhibitory effect of miR-3613 on biological function of gastric cells. Collectively, the data demonstrated that miR-3613 regulates gastric cancer cell by targeting SOCS4, which is expected to be an attractive target for the development of new drugs for the treatment of gastric cancer.

scholarly journals Long Noncoding RNA KLF3-AS1 Acts as an Endogenous RNA of miR-223 to Attenuate Gastric Cancer Progression and Chemoresistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Houxiang Jiang ◽  
KaiFeng Hu ◽  
Yabing Xia ◽  
Linhu Liang ◽  
Xiaoli Zhu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Inhibitory Effects ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Proliferation

Gastric cancer is a deadly disease, and the low rate of early diagnosis and chemoresistance largely contributed to the poor prognosis of gastric cancer. LncRNAs have been extensively reported for their roles in regulating cancer progression. In this study, we found that KLF3-AS1 was down-regulated in gastric cancer cells. Overexpression of KLF3-AS1 repressed gastric cancer cell proliferation, growth. In addition, KLF3-AS1 overexpression also exerted inhibitory effects on the gastric cancer cell invasion, migration and EMT, but promoted chemosensitivity of gastric cancer cells to cisplatin. The mechanistic studies showed that KLF3-AS1 could act as the “sponge” for miR-223 and to repress miR-223 expression in gastric cancer cells. Overexpression of miR-223 reversed the inhibitory effects of KLF3-AS1 overexpression on gastric cancer cell proliferation, invasion, migration and EMT, and attenuated the enhanced effects of KLF3-AS1 overexpression on gastric cancer cell chemosensitivity to cisplatin. The in vivo studies showed that KLF3-AS1 overexpression suppressed the tumor growth of SGC-7901 in the nude mice. In conclusion, our results for the first time demonstrated that KLF3-AS1 was down-regulated in gastric cancer cells and repressed gastric cancer cell proliferation, invasion, migration and EMT, and enhanced chemosensitivity to cisplatin. Further mechanistic results indicated that KLF3-AS1 exerted its biological function in gastric cancer cells by inhibiting miR-223 expression. Future studies are still required to decipher the detailed molecular mechanisms of KLF3-AS1 in gastric cancer.

scholarly journals circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Yue Ma ◽  
Yanyi Ren ◽  
Huitao Wen ◽  
Chengcheng Cui
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Microrna Sponge ◽  
And Function

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

scholarly journals miR-504 Promoted Gastric Cancer Cell Proliferation and Inhibited Cell Apoptosis by Targeting RBM4

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yi Zhang ◽  
Hongmei Yong ◽  
Jing Fu ◽  
Guangyi Gao ◽  
Huichang Shi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Gastric Cancer Cell ◽  
Normal Group ◽  
Cancer Cell Proliferation ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Proliferation

Background. The purpose of this study was to explore the role and underlying mechanism of miR-504 and RBM4 in gastric cancer. Methods. The qRT-PCR or Western blot was performed to determine the expressions of miR-504 and RBM4 in the gastric cancer tissues and normal tissues. Human SGC-7901 cells were transfected with miR-504 mimic/inhibitor or pcDNA-RBM4. Cell proliferation and cell apoptosis were assessed by colony formation assay and flow cytometry, respectively. Luciferase reporter gene assays were used to investigate interactions between miR-504 and RBM4 in SGC-7901 cells. Results. The relative expression of miR-504 was significantly upregulated in the gastric cancer group ( n = 25 ) than in the paired normal group ( n = 25 ), but the relative RBM4 expression was remarkably downregulated in the gastric tumor group, compared with the normal group. Additionally, miR-504 overexpression increased the viability of gastric cancer cells. Moreover, RBM4 is a functional target of miR-504 in gastric cancer cells. miR-504 was further confirmed to promote SGC-7901 cell proliferation and inhibit cell apoptosis by downregulation RBM4 in vitro. Conclusions. miR-504 promotes gastric cancer cell proliferation and inhibits cell apoptosis by targeting RBM4, and this provides a potential diagnostic biomarker and treatment for patients with gastric cancer.

scholarly journals Immune suppressed tumor microenvironment by exosomes derived from gastric cancer cells via modulating immune functions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan Liu ◽  
Shaoxian Wu ◽  
Xiao Zheng ◽  
Panpan Zheng ◽  
Yuanyuan Fu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Lines ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines

Abstract Gastric cancer is one of the leading causes of cancer-related death due to late diagnosis with high metastatic frequency. In this study, the impact of tumor secreted exosomes on immune function in the tumor environment was investigated using exosomes isolated from gastric cancer cell lines MKN-28, MKN-45, and SGC-7901. Results show that exosomes derived from all of these cell lines changed the gene expression and cytokine secretion levels of CD8+ T cells. They also block cell cycle progression, induced apoptosis in CD8+ T cells. Image analysis of fluorescent labeled exosomes derived from three cell lines injected systemically into C57BL/6 mice revealed these exosomes primarily localize to the lungs. We further showed exosomes were mainly taken up by natural killer cells and macrophages in the lung. After long-term exposure to inject exosomes from MKN-45 cells, mice developed an immunosuppressive tumor microenvironment in the lung with increased frequency of effector memory CD4+ T and MDSC, decreased CD8+ T cell and NK frequency. This immune suppressive environment promotes gastric cancer lung metastasis. Lung metastasis sites developed after mice were exposed to exosomes isolated from all three gastric cancer cell lines when the mice were injected with MFC cells. Results suggest that exosomes derived from gastric cancer cells (especially MKN-45 and MKN-28) changed CD8+ T cell gene expression and cytokine secretion patterns to create an immunosuppressive condition for metastatic niche formation in the lung. Overall, this study provides new insights into how gastric cancer derived exosomes modulate the immune response to promote lung tumor metastasis.

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.

Effect of p-PAQR3Thr32 on PD-L1 expression and immune evasion in gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Zhi-Qiang Ling
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Expression Level ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines

e15571 Background: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in some solid tumors. We have now examined PD-L1 expression and its regulation in gastric cancer with p-PAQR3Thr32 protein. Methods: The expression of PD-L1 at the protein and mRNA levels in gastric cancer cell lines was examined by flow cytometry, real-time RT-PCR and western blot analysis, respectively. The expression of PD-L1 and p-PAQR3Thr32 protein in 319 surgically resected gastric cancer specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in gastric cancer cell lines positive for p-PAQR3Thr32 protein induced by glucose starvation than in those negative for the p-PAQR3Thr32 protein. Forced expression of p-PAQR3Thr32 protein in gastric cancer cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in p-PAQR3Thr32 protein positive gastric cancer cells was attenuated by treatment with PAQR3 siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the IRF1 and STAT1 in IFNs-PDL1 signaling pathway in gastric cancer cells positive for p-PAQR3Thr32 protein. At clinical tissue level, the expression level of PD-L1 was positively associated with the presence of p-PAQR3Thr32 protein in gastric cancer specimens. Moreover, the expression level of p-PAQR3Thr32 protein was negatively correlated with CD3, CD8, GZMA (CD8 T cell secretory factor) and positively correlated with CD68 (macrophage marker). Conclusions: Our findings that p-PAQR3Thr32 protein induced by glucose deficiency upregulate PD-L1 by activating IFNs-PDL1 signaling pathway in gastric cancer reveal a direct link between p-PAQR3Thr32 protein and PD-L1 expression. It is suggested that p-PAQR3Thr32 protein may be involved in tumor immunosuppression by inhibiting the proliferation and activity of CD8 T cells in gastric cancer tissues.

Identification of novel 3-nitroacridines as autophagy inducers in gastric cancer cells

2017 ◽  
Vol 41 (10) ◽  
pp. 4087-4095
Author(s):  
Jia Yu ◽  
Xiaoqing Zhao ◽  
Nanmengzi Zhang ◽  
Chaoqun You ◽  
Gang Yao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Gastric Cancer Cells ◽  
Cell Death Pathway ◽  
Gastric Cancer Cell Proliferation

Nine novel 3-nitroacridines were synthesized, of which 3 compounds inhibited gastric cancer cell proliferation via an autophagy-associated cell death pathway.

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