scholarly journals SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Gastric Cancer Cells ◽  
Anion Transporter ◽  
Transporter Family ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

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.

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.

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 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 The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer

2017 ◽  
Vol 42 (5) ◽  
pp. 1739-1754 ◽  
Author(s):  
Lu Zhang ◽  
Jianghao Xu ◽  
Xuan Zhang ◽  
Yi Zhang ◽  
Lu Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Foxp3 Expression ◽  
Migration And Invasion ◽  
Published Data ◽  
Rt Pcr ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Background/Aims: There is little published data on the role of FOXP3 in gastric cancer. Methods: FOXP3 expression and localization in gastric cancer tissues and cells were examined by immunohistochemistry, RT-PCR, flow cytometry, western blot, and laser confocal microscopy. CCK8, plate clone, wound healing, and transwell insert assays were performed for gastric cancer cells. Potential molecules and signaling pathways were screened using high-throughput transcriptome sequencing. Results: FOXP3 expression in gastric cancer tissues was higher than that in para-carcinoma tissues. It was restricted to the cytoplasm of para-carcinoma tissues, but was observed in the cytoplasm or/and nuclei of gastric cancer tissues. FOXP3 expression was positively correlated with pathological grading, and was detected in gastric cancer and GES-1 cells, where it was expressed in the cytoplasm alone, or in both the cytoplasm and the nucleus. FOXP3 overexpression promoted cell proliferation, migration, and invasion, while FOXP3 knockdown suppressed these effects. Furthermore, RT-PCR and ELISA confirmed that FOXP3 upregulation resulted in increased TGF-β expression and secretion in gastric cancer cells. Conclusion: FOXP3 expression was associated with degree of gastric cancer differentiation. In addition, upregulated and ectopic tumoral FOXP3 can promote gastric cancer proliferation, migration, and invasion, partly through the TGF-β pathway.

scholarly journals Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country

2021 ◽  
Vol 22 (2) ◽  
pp. 648
Author(s):  
Catarina Lopes ◽  
Carina Pereira ◽  
Mónica Farinha ◽  
Rui Medeiros ◽  
Mário Dinis-Ribeiro
Keyword(s):  
Gastric Cancer ◽  
Prostaglandin E2 ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Intermediate Risk ◽  
Multifactor Dimensionality Reduction Analysis ◽  
Allelic Discrimination ◽  
Anion Transporter ◽  
Transporter Family ◽  
Increased Risk

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway exerts deleterious pleiotropic effects in inflammation-induced gastric carcinogenesis. We aimed to assess the association of genetic variants in prostaglandin-endoperoxide synthase 2 (PTGS2), ATP binding cassette subfamily C member 4 (ABCC4), hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), and solute carrier organic anion transporter family member 2A1 (SLCO2A1) PGE2 pathway-related genes with gastric cancer (GC) risk in a European Caucasian population. A hospital-based case-control study gathering 260 GC cases and 476 cancer-free controls was implemented. Using a tagSNP approach, 51 single nucleotide polymorphisms (SNPs) were genotyped through MassARRAY® iPLEX Gold Technology or allelic discrimination by real-time polymerase chain reaction (PCR). Homozygous carriers of the minor allele for both rs689466 and rs10935090 SNPs were associated with a 2.98 and 4.30-fold increased risk for GC, respectively (95% confidence interval (CI): 1.14–7.74, p = 0.027; 95% CI: 1.22–15.16, p = 0.026), with the latter also being associated with an anticipated diagnosis age. A multifactor dimensionality reduction analysis identified an overall three-factor best interactive model composed of age, rs689466, and rs1678374 that was associated with a 17.6-fold GC increased risk (95% CI: 11.67–26.48, p < 0.0001, (cross-validation) CV consistency of 8/10 and accuracy of 0.807). In this preliminary study, several tagSNPs in PGE2 pathway-related genes were identified as risk biomarkers for GC development. This approach may help to identify higher-risk individuals and may contribute to the tailoring screening of GC in intermediate-risk European countries.

scholarly journals miR-1290 stimulates proliferation of gastric cancer by targeting SP1 with overexpression of fucosyltransferase IV and α1, 3-fucosylated glycans

2020 ◽  
Author(s):  
Faisal Aziz ◽  
Li Yulin ◽  
Qiu Yan
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Specific Protein ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
H Pylori ◽  
Dose Dependent ◽  
Development Of Gastric Cancer

AbstractFucosylation plays an important role in the development of carcinogenesis. miRNA-1290 emerged as crucial molecule to regulate cancer cell proliferation. This study evaluated the role of miRNA-1290 to development of gastric cancer by regulation of fucosyltransferase-IV, specific protein-1 (SP1) and α1,3-fucosylated glycans.We analyzed the role of H. pylori and miR-1290 in gastric cancer cells in induce fucosylation and cell proliferation, as well as SP1 and ubiquitin protein interaction. We found miR-1290 induced proliferation in H. pylori CagA treated gastric cancer cells by stimulating FUT4/LeY fucosylation, as evidence by high expression of miR-1290 and phosphorylation of EGFR and MAPKs pathway in dose–dependent manner. In addition, miR-1290 inhibited SP1 protein with the regulation of ubiquitin-proteasomal system and leads to stimulate FUT4 and α1,3-fucosylated glycans level. We report the role of miRNA-1290 to stimulate FUT4 fucosylation and LeY through EGFR/MAPKs pathway by targeting SP1 in the development of gastric cancer.

scholarly journals Diosgenin inhibits the proliferation of gastric cancer cells via inducing mesoderm posterior 1 down-regulation-mediated alternative reading frame expression

2021 ◽  
pp. 096032712110532
Author(s):  
Lin Gu ◽  
Hailun Zheng ◽  
Rui Zhao ◽  
Xiaojing Zhang ◽  
Qizhi Wang
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Reading Frame ◽  
Anti Cancer ◽  
Cancer Tissues ◽  
Alternative Reading

Introduction Whether and how mesoderm posterior 1 (MESP1) plays a role in the proliferation of gastric cancer cells remain unclear. Methods The expression of MESP1 was compared in 48 human gastric cancer tissues and adjacent normal tissues. Knockdown of MESP1 was performed to investigate the role of MESP1 in the proliferation and apoptosis of BGC-823 and MGC-803 gastric cancer cells. Knockdown of alternative reading frame (ARF) was performed to study the role of ARF in the inhibitory effect of MESP1 knockdown on cell proliferation in gastric cancer cells. Mouse subcutaneous xenograft tumor model bearing BGC-823 cells was used to investigate the role of MESP1 in the growth of gastric tumor in vivo. The effect of seven active ingredients from T. terrestris on MESP1 expression was tested. The anti-cancer effect of diosgenin was confirmed in gastric cancer cells. MESP1 dependence of the anti-cancer effect of diosgenin was confirmed by MESP1 knockdown. Results MESP1 was highly expressed in human gastric cancer tissues ( p < 0.05). MESP1 knockdown induced apoptosis and up-regulated the expression of ARF in gastric cancer cells ( p < 0.05). Knockdown of ARF attenuated the anti-cancer effect of MESP1 knockdown ( p < 0.05). In addition, MESP1 knockdown also suppressed tumor growth in vivo ( p < 0.05). Diosgenin inhibits both mRNA and protein expression of MESP1 ( p < 0.05). MESP1 knockdown attenuated the anti-cancer effect of diosgenin ( p < 0.05). Conclusions MESP1 promotes the proliferation of gastric cancer cells via inhibiting ARF expression. Diosgenin exerts anti-cancer effect through inhibiting MESP1 expression in gastric cancer cells.

scholarly journals LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
An Yang ◽  
Xin Liu ◽  
Ping Liu ◽  
Yunzhang Feng ◽  
Hongbo Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines ◽  
Development Of Gastric Cancer

Abstract Background Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. Methods The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. Results UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. Conclusions UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

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