DEPDC1 upregulation promotes cell proliferation and predicts poor prognosis in patients with gastric cancer

2020 ◽  
pp. 1-9
Author(s):  
Zhaohua Gong ◽  
Hongjin Chu ◽  
Jian Chen ◽  
Lixin Jiang ◽  
Benjiao Gong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Gastric Adenocarcinoma ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Mrna Level ◽  
Tumor Development ◽  
Kaplan Meier

BACKGROUND: Previous studies revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis and progression of several types of human cancer. However the role of DEPDC1 in gastric cancer has not been studied. OBJECTIVE: The objective of this study was to study the expression and pathophysiological function of DEPDC1 in gastric cancer. METHODS: DEPDC1 expression in gastric adenocarcinoma cells was examined with Western blot and qRT-PCR. Clinical pathological features of patients were determined by immunohistochemistry. The effect of DEPDC1 expression on cell proliferation was studied by in vitro cell proliferation assay; and cell cycle influence was assessed by ow cytometry. Survival curves were plotted using Kaplan-Meier. RESULTS: DEPDC1 was overexpressed in gastric adenocarcinoma tissues compared with the paired adjacent normal gastric tissues, in accordance with mRNA level downloaded from GEPIA database. DEPDC1 expression level was significantly associated with cancer metastasis and differentiation. DEPDC1 upregulation caused cell cycle accelerating from G1 to S phase, and it was correlated with poorer overall survival. CONCLUSION: Therefore, DEPDC1 upregulation in gastric adenocarcinoma is associated with tumor development and poor clinical outcomes of the patients, implying DEPDC1 might be a potential therapeutic target against gastric cancer.

scholarly journals PHF14 Promotes Cell Proliferation and Migration through the AKT and ERK1/2 Pathways in Gastric Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuzu Zhao ◽  
Jiang He ◽  
Yongsen Li ◽  
Man Xu ◽  
Xingzhi Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tumor Promoter ◽  
Clinical Samples ◽  
Gastric Cancer Cells ◽  
Phosphorylated Akt

PHF14 is a new member belonging to PHD finger proteins. PHF14 is involved in multiple biologic processes including Dandy–Walker syndrome, mesenchyme growth, lung fibrosis, renal fibrosis, persistent pulmonary hypertension, and tumor development. This study aims to explore whether PHF14 plays an important role in gastric cancer. Here, PHF14 is indicated as a tumor promoter. The expression of PHF14 enhances no matter in clinical samples or in gastric cancer cells. High expression of PHF14 impairs survival of patients. Attenuation of PHF14 inhibits cell proliferation in gastric cancer cells. PHF14 downregulation inhibits the expression of cell cycle-related proteins, CDK6 and cyclin D1. Furthermore, silencing of PHF14 reduces the level of phosphorylated AKT as well as phosphorylated ERK1/2. Finally, downregulation of PHF14 in gastric cancer cells inhibits colony formation in vitro and tumorigenesis in vivo. These results indicate that PHF14 promotes tumor development in gastric cancer, so PHF14 thereby acts as a potential target for gastric cancer therapy.

scholarly journals Insulin Stimulates Goose Liver Cell Growth by Activating PI3K-AKT-mTOR Signal Pathway

2016 ◽  
Vol 38 (2) ◽  
pp. 558-570 ◽  
Author(s):  
Chunchun Han ◽  
Shouhai Wei ◽  
Qi Song ◽  
Fang He ◽  
Xiangping Xiong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Protein Content ◽  
Mrna Level ◽  
Signal Pathway ◽  
Mtor Pathway ◽  
Brdu Incorporation ◽  
Primary Hepatocytes

Background/Aims: Recent studies have suggested a crucial role for PI3K-Akt-mTOR pathway in regulating cell proliferation, so we hypothesize that insulin acts goose hepatocellular growth by PI3K-Akt-mTOR signal pathway. Because the physiological status of liver cells in vitro is different from that in vivo, a simplified cell model in vitro was established. Methods: Goose primary hepatocytes were isolated and incubated in either no addition as a control or insulin or PI3K-Akt-mTOR pathway inhibitors or co-treatment with glucose and PI3K-Akt-mTOR pathway inhibitors; Then, cell DNA synthesis and cell cycle analysis were detected by BrdU-incorporation Assay and Flow cytometric analysis; the mRNA expression and protein expression of factors involved in the cell cycle were determined by Real-Time RT-PCR, ELISA, and western blot. Results: Here we first showed that insulin evidently increased the cell DNA synthesis, the mRNA level and protein content of factors involved in the cell proliferation of goose primary hepatocytes. Meanwhile, insulin evidently increased the mRNA level and protein content of factors involved in PI3K-Akt-mTOR pathway. However, the up-regulation of insulin on cell proliferation was decreased significantly by the inhibitors of PBK-Akt-mTOR pathway, LY294002, rapamycin or NVP-BEZ235. Conclusion: These findings suggest that PI3K-Akt-mTOR pathway plays an essential role in insulin-regulated cell proliferation of goose hepatocyte.

scholarly journals Cyclin D3-CDK6 Complex Facilitates Tumorigenesis by Regulating the C-Myc/miR-15a/16 Axis in a Feedback Loop in Gastric Cancer

2020 ◽  
Author(s):  
Yeting Hong ◽  
Wei He ◽  
Jianbin Zhang ◽  
Lu Shen ◽  
Chong Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cyclin D3 ◽  
Luciferase Reporter

Abstract Background: Cyclin D3-CDK6 complex is a component of the core cell cycle machinery that regulates cell proliferation. By using Human Protein Atlas database, a higher expression level of this complex was found in gastric cancer. However, the function of this complex in gastric cancer remain poorly understood. This study aims to determine the expression pattern of this complex in gastric cancer and to investigate its biological role during tumorigenesis.Methods: To demonstrate that Cyclin D3-CDK6 regulate the c-Myc/miR-15a/16 axis in a feedback loop in gastric cancer, a series of methods were conducted both in vitro and in vivo experiments, including qRT-PCR, western blot analysis, EdU assay, flow cytometry, luciferase reporter assay and immunohistochemical staining. SPSS and Graphpad prism software were used for data analysis.Results: In this study, we found that Cyclin D3 and CDK6 were significantly upregulated in gastric cancer and correlated with poorer overall survival. Further study proved that this complex significantly promoted cell proliferation and cell cycle progression in vitro and accelerated xenografted tumor growth in vivo. Furthermore, we explored the molecular mechanisms through which the complex mediated Rb phosphorylation and then promoted c-Myc expression in vitro, we also found c-Myc could suppress miR-15a/16 expression in gastric cancer cell. Finally, we found that miR-15a/16 can simultaneously regulate Cyclin D3 and CDK6 expression as direct target genes.Conclusions: Our findings uncover the Cyclin D3-CDK6/c-Myc/miR-15a/16 feedback loop axis as a pivotal role in the regulation of gastric cancer tumorigenesis, and this regulating axis may provide a potential therapeutic target for gastric cancer treatment.

Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer

Gut ◽  
2019 ◽  
Vol 68 (10) ◽  
pp. 1764-1773 ◽  
Author(s):  
Chao Lin ◽  
Hongyong He ◽  
Hao Liu ◽  
Ruochen Li ◽  
Yifan Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Cancer Metastasis ◽  
Tumour Progression ◽  
Mrna Level ◽  
Immune Surveillance ◽  
Therapeutic Effects ◽  
High Level ◽  
Cancer Tissues

ObjectiveOur previous studies have identified CXCL8 as the crucial chemokine responsible for gastric cancer metastasis mediated by loss of RACK1. However, the regulatory effect of CXCL8 on immune surveillance in gastric cancer remains obscure.DesignFlow cytometry analyses were performed to examine major source of CXCL8 and phenotypes of immune cells in fresh tumour tissues from 76 patients with gastric cancer. Real-time PCR was performed to analyse CXCL8 mRNA level in gastric cancer tissues. For immunohistochemical analyses, a total of 420 patients with gastric cancer undergoing curative resection were enrolled. In vitro culture of fresh tumour tissue was performed to evaluate the potential therapeutic effect of blocking CXCL8 pathway in gastric cancer.ResultsIncreased level of CXCL8 indicates poor clinical outcome and tumour progression in patients with gastric cancer. In gastric cancer tissues, CXCL8 is predominantly secreted by macrophages and colony stimulating factor 2 (CSF-2) facilitates macrophage-derived CXCL8 secretion. High level of CXCL8 is associated with decreased CD8+ T cells infiltration and Ki67+ CD8+ T cells proportion. Moreover, CXCL8 also inhibits CD8+ T cells function by inducing the expression of PD-L1 on macrophages. Finally, we show that a small-molecule CXCR2 inhibitor, reparixin, drives the decreased programmed death-ligand 1 (PD-L1+) macrophages and promotes antitumour immunity. Accordingly, high levels of CXCL8+ macrophages are positively correlated with poor prognosis in patients with gastric cancer.ConclusionsCXCL8 is predominantly secreted by macrophages and contributes to the immunosuppressive microenvironment by inducing PD-L1+ macrophages in gastric cancer. CXCL8 inhibitors may drive antitumour response, providing potential therapeutic effects for patients with gastric cancer.

scholarly journals Dysregulation of miR-23b-5p promotes cell proliferation via targeting FOXM1 in hepatocellular carcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xinchen Yang ◽  
Shikun Yang ◽  
Jinhua Song ◽  
Wenjie Yang ◽  
Yang Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Tumor Development ◽  
Loss Of Function ◽  
Cycle Arrest ◽  
Cell Proliferation Inhibition

AbstractGrowing evidence demonstrates that MicroRNAs (miRNAs) play an essential role in contributing to tumor development and progression. However, the underlying role and mechanisms of miR-23b-5p in hepatocellular carcinoma (HCC) formation remain unclear. Our study showed that miR-23b-5p was downregulated in the HCC tissues and cell lines, and lower expression of miR-23b-5p was associated with more severe tumor size and poorer survival. Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in HCC specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p. In addition, miR-23b-5p could regulate cyclin D1 and c-MYC expression by directly targeting FOXM1. Further study revealed that restoration of FOXM1 neutralized the cell cycle arrest and cell proliferation inhibition caused by miR-23b-5p. Taken together, our findings suggest that miR-23b-5p acted as a tumor suppressor role in HCC progression by targeting FOXM1 and may serve as a potential novel biomarker for HCC diagnosis and prognosis.

scholarly journals LncRNA AFAP1-AS1 is a prognostic biomarker and serves as oncogenic role in retinoblastoma

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Fengqin Hao ◽  
Yanan Mou ◽  
Laixia Zhang ◽  
Shuna Wang ◽  
Yang Yang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Human Cancer ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Retinoblastoma Cell ◽  
Choroidal Invasion

The actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been found to serve as an oncogenic long noncoding RNA (lncRNA) in most types of human cancer. The role of AFAP1-AS1 in retinoblastoma remains unknown. The purpose of the present study is to explore the clinical significance and biological function of AFAP1-AS1 in retinoblastoma. Levels of AFAP1-AS1 expression were measured in retinoblastoma tissues and cell lines. Loss-of-function study was performed to observe the effects of AFAP1-AS1 on retinoblastoma cell proliferation, cell cycle, migration, and invasion. In our results, AFAP1-AS1 expression was elevated in retinoblastoma tissues and cell lines, and associated with tumor size, choroidal invasion, and optic nerve invasion. Moreover, high expression of AFAP1-AS1 was an independent unfavorable prognostic factor in retinoblastoma patients. The experiment in vitro suggested down-regulation of AFAP1-AS1 inhibited retinoblastoma cell proliferation, migration and invasion, and blocked cell cycle. In conclusion, AFAP1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

scholarly journals Systematic Identification of Key Functional Modules and Genes in Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Rui Wu ◽  
Jin-Yu Sun ◽  
Li-Li Zhao ◽  
Zhi-Ning Fan ◽  
Cheng Yang
Keyword(s):  
Gastric Cancer ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Human Cancer ◽  
Differentially Expressed Gene ◽  
Hub Gene ◽  
Kaplan Meier ◽  
Incidence And Mortality ◽  
High Incidence ◽  
Systematic Identification

Gastric cancer (GC) is associated with high incidence and mortality rates worldwide. Differentially expressed gene (DEG) analysis and weighted gene coexpression network analysis (WGCNA) are important bioinformatic methods for screening core genes. In our study, DEG analysis and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the DEGs. SBNO2 was identified as the hub gene based on the intersection between the DEGs and the purple module in WGCNA. The expression and prognostic value of SBNO2 were verified in UALCAN, GEPIA2, Human Cancer Metastasis Database, Kaplan–Meier plotter, and TIMER. We identified 1974 DEGs, and 28 modules were uncovered via WGCNA. The purple module was identified as the hub module in WGCNA. SBNO2 was identified as the hub gene, which was upregulated in tumour tissues. Moreover, patients with GC and higher SBNO2 expression had worse prognoses. In addition, SBNO2 was suggested to play an important role in immune cell infiltration. In summary, based on DEGs and key modules related to GC, we identified SBNO2 as a hub gene, thereby offering novel insights into the development and treatment of GC.

scholarly journals LINC00518 Promotes Cell Proliferation by Regulating the Cell Cycle of Lung Adenocarcinoma Through miR-185-3p Targeting MECP2

2021 ◽  
Vol 11 ◽  
Author(s):  
Xu Han ◽  
Jixiang Wu ◽  
Yajun Zhang ◽  
Jianxiang Song ◽  
Zhan Shi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Human Cancer ◽  
Survival Rates ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.

Dextran sulfate inhibits cell proliferation and induces apoptosis by regulating EZH2 in gastric carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Yunning Huang ◽  
Wenjun Wang ◽  
Yuan-Yi Xu ◽  
Jiaxin Guo ◽  
Longxing Jiao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Dextran Sulfate ◽  
Human Cancer ◽  
Critical Role ◽  
Nuclear Antigen ◽  
Gastric Cancer Cells ◽  
Bioinformatics Analyses ◽  
Gastrointestinal Malignancies

Background: Gastric cancer (GC) is one of the most common gastrointestinal malignancies. According to reports, the enhancer of zeste homolog 2 (EZH2) exhibits carcinogenic function in a variety of cancers. Therefore, EZH2 may be a potential therapeutic target for the treatment of human cancer. Macromolecular dextran sulfate (DS) has been displayed to play a critical role in tumor inhibition. However, the molecular mechanism by which DS mediates this effect is unclear. Objectives: In this study, we explored the effects of DS on the proliferation and apoptosis of gastric cancer and the related mechanisms. Cell proliferation and counting assays, as well as cell colony formation assays, revealed that DS inhibited the proliferation and tumorigenesis of GC cells. Additionally, flow cytometry analysis displayed that DS blocked the cell cycle of GC cells in the G1/S phase and promoted their apoptosis. Methods: Bioinformatics analyses, enzyme-linked immunosorbent assays, immunohistochemistry, and other methods were applied to measure the expression of EZH2 in human GC cells and tissues. Results and Discussion: Further studies have shown that DS treatment can reduce the expression of proliferating cell nuclear antigen (PCNA) and increase the level of the ratio of Bax: Bcl-2 protein in GC cells. In addition, DS reduced EZH2 levels and increased CXXC finger protein 4 levels both in vitro and in vivo. In addition, down-regulation of EZH2 with EZH2 inhibitors reversed the inhibitory effect of DS on gastric cancer cells. Conclusion: Collectively, our work demonstrates that DS suppresses proliferation and promotes apoptosis of GC cells by regulating EZH2. Our study suggests that DS is a promising therapeutic compound for the treatment of GC.

Sign in / Sign up

Export Citation Format

Share Document