scholarly journals NLRP3 is Highly Expressed in Stomach Adenocarcinoma and May Serve as a Novel Prognostic Biomarker

2021 ◽  
Author(s):  
Chenxi Yuan ◽  
Qingwei Wang ◽  
Yipeng Song ◽  
Jinming Yu
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Regression Analysis ◽  
Immune Cells ◽  
Cox Regression ◽  
Normal Tissues ◽  
Stomach Adenocarcinoma ◽  
Clinicopathologic Parameters ◽  
Nlrp3 Expression

Abstract Background: Stomach adenocarcinoma (STAD) is a common cancer type around the world. The prognosis in advanced patients is poor. Since NLRP3 was not extensively studied in the field of tumor, so we aimed to identify the impact of NLRP3 on STAD by bioinformatics analyses and in vitro experiments. Methods: TCGA , kaplan-Meier Plotter and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of gastric carcinoma patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Finally, we verified the NLRP3 expression in paired gastric cancer tissues and adjacent normal tissues by western blot and q-PCR. We also constructed NLRP3 overexpression model in gastric cancer cell line and observed cell proliferation ability.Results: NLRP3 expressed disparately in gastric tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for bad prognosis in STAD. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with unfavorable clinicopathologic parameters such as higher T stage, higher histologic grade and worse survival outcome. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with poor prognosis, unfavorable clinicopathologic parameters and increased proportion of immune cells in STAD. In vitro analysis revealed that cell proliferation ability was enhanced in gastric cancer cells trasnfected with NLRP3 overexpression. These conclusions indicate that NLRP3 has great potential to serve as a biomarker for evaluating prognosis in patients diagnosed with gastric carcinoma.

scholarly journals Regulation of Apelin Is Associated with Proliferation and Angiogenesis in Gastric Cancer

2020 ◽  
Author(s):  
LiJun Tian ◽  
Hong-Zhi Liu ◽  
Qiang Zhang ◽  
Dian-Zhong Geng ◽  
Jing Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cox Regression ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background: Apelin is an emerging endogenous ligand, which is involved in proliferation and angiogenesis in certain cancers. However, few studies have reported its functions and underlying mechanisms in human gastric cancer (GC). Therefore, the present study aimed to investigate the effect of Apelin expression in human GC and the underlying mechanisms of Apelin in the promotion of proliferation both in vitro and in vivo.Methods: A total of 178 patients diagnosed with GC under postoperative care were enrolled for the study to investigate clinicopathological and immunohistochemical factors of Apelin expression. Survival of patients was analyzed using the Kaplan-Meier method and Cox regression model. We adopted quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA to analyze human GC specimens and cell lines. The role and mechanisms of Apelin were evaluated by performing in vitro and in vivo experiments to analyze exogenous Apelin and its overexpression in human GC cells. Results: The expression of Apelin was higher in human gastric cancer cells than in adjacent normal tissues. Apelin, which was overexpressed in vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) status (P <0.05), pathological type (P <0.05) and nerve invasion (P <0.05), also exhibited a positive correlation with vascular endothelial growth factor (VEGF). Apelin overexpression or exogenous Apelin activated downstream of ERK/Cyclin D1/MMP-9 signaling pathway to promote MGC-803 cell proliferation and invasion in vitro. Apelin overexpression promoted angiogenesis aiming at accelerating growth of subcutaneous xenograft in vivo.Conclusions: This study has elucidated the relationship between Apelin and its clinicopathological features in human GC, and the role of Apelin in tumor cell proliferation in human GC cell lines. This is the first study to elucidate underlying mechanisms of Apelin in the proliferation of GC. Apelin can be a potential therapeutic target for human GC.

NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma

2021 ◽  
Author(s):  
Chenxi Yuan ◽  
Qingwei Wang ◽  
Xueting Dai ◽  
Yipeng Song ◽  
Jinming Yu
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Immune Cells ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
The Impact ◽  
Nlrp3 Expression

Abstract Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.

scholarly journals Apelin Over-Expression Promotes Proliferation and Angiogenesis of Gastric Cancer Cells

2021 ◽  
Author(s):  
Li-Jun Tian ◽  
Hong-Zhi Liu ◽  
Qiang Zhang ◽  
Dian-Zhong Geng ◽  
Jing Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cox Regression ◽  
Gastric Cancer Cells ◽  
Over Expression ◽  
Normal Tissues

Abstract Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.

scholarly journals MicroRNA-99b predicts clinical outcome of osteosarcoma and suppresses tumor cell proliferation, migration and invasion

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Prognostic Value ◽  
Cox Regression ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.

scholarly journals Transcription Elongation Factor A-like 7 is a Stemness-Related Prognostic Factor in Gastric Cancer

2021 ◽  
Author(s):  
Haisheng Qian ◽  
Xin Gao ◽  
Rui Ma ◽  
Wenjie Li ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Cox Regression ◽  
Learning Algorithm ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Significant Difference ◽  
Selection Operator ◽  
Level Group

Abstract Background: Stemness is described as the potential for self-renewal and differentiation from the cell-of-origin. A previous study calculated the mRNA expression-based stemness index (mRNAsi) based on a one-class logistic regression machine learning algorithm for describing stemness features of cancer. We aim to identify stemness-related prognostic genes in gastric cancer (GC) based on mRNAsi using bioinformatics analysis.Methods: The WGCNA analysis was performed to find the relevant gene modules to mRNAsi. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways annotation analysis were performed on genes in blue module. The overall survival analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were used to identify prognostic genes highly associated with survival. The multivariate Cox regression analysis was performed to analysis prognostic factors. The nomogram was constructed according to the result of multivariate analysis. qPCR, Western Blot and IHC staining were appliedResults: The mRNAsi of tumors is higher than normal tissues, and there was a significant difference in overall survival (OS) between the high and low mRNAsi GC groups. TCEAL7 was selected to be the key gene associated with mRNAsi and prognosis according to the result of least absolute shrinkage and selection operator (LASSO) Cox regression. The expression level of TCEAL7 was lower in tumors than in normal tissues, but high TCEAL7 level group showed a worse OS than low TCEAL7 level group in GC. Based on the result of multivariable Cox regression analysis which including TCEAL7 and clinical characteristics, a nomogram for predicting GC 1-, 3-, and 5-year survival was established. The C-index and the AUC (Area Under Curve) of the model indicated that the model has a good discrimination ability. Additionally, the calibration curves of 3- and 5-year OS rates showed the model fits well. The experimental validation of the expression of TCEAL7 in GC and normal tissues were consistent with the above.Conclusions: In summary, we verified mRNAsi was associated with the prognosis of GC patients. And TCEAL7 was finally identified as the key gene correlated with stemness features and prognosis in GC.

scholarly journals Apelin Over-Expression Promotes Proliferation and Angiogenesis of Gastric Cancer Cells

2021 ◽  
Author(s):  
LiJun Tian ◽  
Hong-Zhi Liu ◽  
Qiang Zhang ◽  
Dian-Zhong Geng ◽  
Jing Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cox Regression ◽  
Gastric Cancer Cells ◽  
Over Expression ◽  
Normal Tissues

Abstract Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.

Single-chain Antibody Against Reg4 Suppresses Gastric Cancer Cell Growth and Enhances 5-FU-induced Cell Death in vitro

2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Ags Cells ◽  
Thiazolyl Blue Tetrazolium Bromide

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.

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.

scholarly journals Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Metabolism ◽  
Vital Role ◽  
Methionine Metabolism ◽  
Promoter Regions ◽  
Normal Tissues ◽  
Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

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