scholarly journals TNFAIP8 inhibits the proliferation of gastric cancer cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy

2020 ◽  
Author(s):  
Zheng Chen ◽  
Jianguo Zhang ◽  
Chenyang Dong ◽  
Dongsheng Li ◽  
Yuehan Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Invasion ◽  
Signal Pathway ◽  
Gastric Cancer Cells ◽  
Mrna And Protein Expression ◽  
Gastric Cancer Cell Lines ◽  
A Cell

Abstract Background : The purpose of this article was to study the role of TNFAIP8 in gastric cancer. Methods : RT-PCR was used to detect the expression of TNFAIP8 mRNA and protein level in normal gastric mucosa cells and four gastric cancer cell lines. TNFAIP8 was silenced or overexpressed in two cell lines, CCK-8 cell viability was used, transwell experiment was used to detect cell invasion capability, and flow cytometry was used to detect cell apoptosis. TNFAIP was silenced or overexpressed in a cell line, and nude mice were inoculated to form transplanted tumors. HE staining and immunohistochemistry staining were used to detect the histopathological changes of tumors. Results : The mRNA and protein expression of TNFAIP8 was significantly up-regulated in GC patients and cells. After silencing and overexpressing TNFAIP8, gastric cancer cells with high expression increased, apoptosis decreased, and cell invasion increased. Expression of mTOR-Akt-ULK1 signal pathway was inhibited and autophagy signal was activated. Conclusions : Our findings indicate that TNFAIP8 inhibited gastric cancer cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

scholarly journals The role of TNFAIP8-mediated mTOR-Akt-ULK1 signaling pathway in gastric cancer

2020 ◽  
Author(s):  
Zheng Chen ◽  
Jianguo Zhang ◽  
Chenyang Dong ◽  
Dongsheng Li ◽  
Yuehan Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Invasion ◽  
Signal Pathway ◽  
Gastric Cancer Cells ◽  
Mrna And Protein Expression ◽  
Gastric Cancer Cell Lines ◽  
A Cell

Abstract Background: The purpose of this article was to study the role of TNFAIP8 in gastric cancer. Methods: RT-PCR was used to detect the expression of TNFAIP8 mRNA and protein level in normal gastric mucosa cells and four gastric cancer cell lines. TNFAIP8 was silenced or overexpressed in two cell lines, CCK-8 cell viability was used, transwell experiment was used to detect cell invasion capability, and flow cytometry was used to detect cell apoptosis. TNFAIP was silenced or overexpressed in a cell line, and nude mice were inoculated to form transplanted tumors. HE staining and immunohistochemistry staining were used to detect the histopathological changes of tumors. Results: The mRNA and protein expression of TNFAIP8 was significantly up-regulated in GC patients and cells. After silencing and overexpressing TNFAIP8, gastric cancer cells with high expression increased, apoptosis decreased, and cell invasion increased. Expression of mTOR-Akt-ULK1 signal pathway was inhibited and autophagy signal was activated. Conclusions: Our findings indicate that TNFAIP8 inhibited gastric cancer cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

scholarly journals Inhibition of mTOR-Akt-ULK1 signaling pathway and activation of autophagy by TNFAIP8 in metastasis of gastric cancer

2020 ◽  
Author(s):  
Zheng Chen ◽  
Jianguo Zhang ◽  
Chenyang Dong ◽  
Dongsheng Li ◽  
Yuehan Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Invasion ◽  
Gastric Cancer Cell ◽  
Signal Pathway ◽  
Rt Pcr ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
A Cell

Abstract Background The purpose of this article is to study the mechanism of TNFAIP8 in gastric cancer. Methods RT-PCR was used to detect the expression of TNFAIP8 mRNA in normal gastric mucosa cells and four gastric cancer cell lines. TNFAIP8 was silenced or overexpressed in two cell lines, CCK-8 cell viability was used, transwell experiment was used to detect cell invasion capability, and flow cytometry was used to detect cell apoptosis. TNFAIP was silenced or overexpressed in a cell line, and nude mice were inoculated to form transplanted tumors. HE staining and immunohistochemistry staining were used to detect the histopathological changes of tumors. Results The expression of TNFAIP8 was significantly up-regulated in GC patients and cells. After silencing and overexpressing TNFAIP8, gastric cancer cells with high expression increased, apoptosis decreased, and cell invasion increased. Expression of mTOR-Akt-ULK1 signal pathway was inhibited and autophagy signal was activated. Conclusions Our findings indicate that TNFAIP8 inhibits the metastasis of gastric cancer cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

scholarly journals TNFAIP8 inhibits gastric cancer proliferation by mTOR-Akt-ULK1 and autophagy signal pathway

2020 ◽  
Author(s):  
Zheng Chen ◽  
Jianguo Zhang ◽  
Chenyang Dong ◽  
Dongsheng Li ◽  
Yuehan Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cell Invasion ◽  
Signal Pathway ◽  
Rt Pcr ◽  
Transplanted Tumors ◽  
Cancer Proliferation ◽  
Mrna And Protein Expression ◽  
A Cell

Abstract Background: The purpose of this article was to study the role of TNFAIP8 in gastric cancer.Methods: RT-PCR was used to detect the expression of TNFAIP8 mRNA and protein level in normal gastric mucosa cells and four gastric cancer (GC) cell lines. TNFAIP8 was silenced or overexpressed in two cell lines, CCK-8 cell viability was used, transwell experiment was used to detect cell invasion capability, and flow cytometry was used to detect cell apoptosis. TNFAIP was silenced or overexpressed in a cell line, and nude mice were inoculated to form transplanted tumors. HE staining and immunohistochemistry staining were used to detect the histopathological changes of tumors. Results: The mRNA and protein expression of TNFAIP8 was significantly up-regulated in GC patients and cells. After silencing and overexpressing TNFAIP8, GC cells with high expression increased, apoptosis decreased, and cell invasion increased. Expression of mTOR-Akt-ULK1 signal pathway was inhibited and autophagy signal was activated. Conclusions: Our findings indicate that TNFAIP8 inhibited GC cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

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.

Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Yu Jin Kim ◽  
Won Shik Kim ◽  
Sang Woo Kim ◽  
Woon Yong Jung
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Early Stage ◽  
Gastric Adenoma ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
And Migration ◽  
Gastric Cancer Patients ◽  
And Function

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

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.

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.

scholarly journals Smad2/3/4 Pathway Contributes to TGF-β-Induced MiRNA-181b Expression to Promote Gastric Cancer Metastasis by Targeting Timp3

2016 ◽  
Vol 39 (2) ◽  
pp. 453-466 ◽  
Author(s):  
Qi Zhou ◽  
Xiao Zheng ◽  
Lujun Chen ◽  
Bin Xu ◽  
Xin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Real Time ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines

Background/Aims: Transforming growth factor beta (TGF-β) plays a major role in tumorigenesis. MicroRNA-181b (miRNA-181b) is a multifaceted miRNA that has been implicated in many cellular processes such as cell fate determination and cellular invasion. This study aimed to confirm the relationship of miRNA-181b and the TGF-β-Smad2/3/4 pathway with the induction of the epithelial-to-mesenchymal transition (EMT) in gastric cancer. Methods: This study investigated the ability of TGF-β to induce migration by wound healing and transwell invasion assays in human gastric cancer cell lines. miRNA expression was altered using miRNA-181b mimic and inhibitor in the same system. Expression of miRNA-181b, the hypothetical target gene Timp3 and EMT-related markers were analyzed by real-time real-time quantitative RT-PCR. Immunoblotting was used to investigate the levels of phospho-Smad2 and Smad4. Dual-luciferase reporter assays were performed to confirm the direct binding of miRNA-181b to Timp3. Results: miRNA-181b was significantly upregulated in response to TGF-β treatment in gastric cancer cell lines. Overexpression of miR-181b mimic induced an in vitro EMT-like change to a phenotype similar to that following TGF-β treatment alone and was reversed by miRNA-181b inhibitor. Inhibition of TGF-β−Smad2/3 signaling with SD-208 significantly attenuated the upregulation of miRNA-181b. Knockdown of Smad4 in gastric cancer cells strongly attenuated the upregulation of miRNA-181b. Moreover, miR-181b was found to directly target the 3′ untranslated region (3′UTR) of Timp3 mRNA affecting TGF-β-induced EMT. Conclusions: Our results elucidate a novel mechanism through which the TGF-β pathway regulates the EMT of gastric cancer cells by increasing the levels of miRNA-181b to target Timp3 via the Smad2/3/4-dependent pathway. These findings provide insights into the cellular and environmental factors regulating EMT, which may guide future studies on therapeutic strategies targeting these cells.

scholarly journals SNAIL regulates gastric carcinogenesis through CCN3 and NEFL

2020 ◽  
Author(s):  
Ru Chen ◽  
Kenji Masuo ◽  
Akitada Yogo ◽  
Shoko Yokoyama ◽  
Aiko Sugiyama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines

Abstract Among cancer cells, there are specific cell populations of whose activities are comparable to those of stem cells in normal tissues, and for whom the levels of cell dedifferentiation are reported to correlate with poor prognosis. Information concerning the mechanisms that modulate the stemness like traits of cancer cells is limited. Therefore, we examined five gastric cancer cell lines and isolated gastric oncospheres from three gastric cancer cell lines. The gastric cancer cells that expanded in the spheres expressed relatively elevated proportion of CD44, which is a marker of gastric cancer stem cells, and displayed many properties of cancer stem cells, for example: chemoresistance, tumorigenecity and epithelial-mesenchymal transition (EMT) acquisition. SNAIL, which is a key factor in EMT, was highly expressed in the gastric spheres. Microarray analysis in gastric cancer cell line HGC27 showed that CCN3 and NEFL displayed the greatest differential expression by knocking down of SNAIL; the former was up-regulated and the latter down-regulated, respectively. Down-regulation of CCN3 and up-regulation of NEFL gene expression impaired the SNAIL-dependent EMT activity: high tumorigenicity, and chemoresistance in gastric cancer cells. Thus, approach that disrupts SNAIL/CCN3/NEFL axis may be credible in inhibiting gastric cancer development.

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