scholarly journals Effect of Linc-00475 Regulation of p53 on Glycolysis and Survival in Gastric Cancer

2021 ◽  
Author(s):  
Chao Zhang ◽  
Shutao Zhao ◽  
Xudong Wang
Keyword(s):  
Gastric Cancer ◽  
Glucose Metabolism ◽  
Western Blot ◽  
Aerobic Glycolysis ◽  
Rank Test ◽  
Cancer Tissue ◽  
Regulatory Relationship ◽  
P53 Expression ◽  
Qrt Pcr ◽  
Area Of Interest

Abstract Background: Abnormal glucose metabolism leading to tumor proliferation and metastasis is an important area of interest in cancer treatment. The purpose of this study was to investigate the effects of clinical expression of glucose metabolism-related genes Linc-00475 and p53 on glycolysis and survival.Methods: A key differential gene Linc-00475 was screened using a metabolic database, and its downstream gene, p53, was predicted. A total of 107 gastric cancer tissue samples from patients diagnosed at our center between 2011 and 2013 were selected. The expression levels of Linc-00475 and p53 were detected via in situ hybridization or immunohistochemistry. Chi-square test was used to analyze the relationship between Linc-00475 and p53 expression and clinicopathological factors. Kaplan-Meier method and log rank test were used to analyze patients’ overall survival. To determine the effect of Linc-00475 on glycolysis, qRT-PCR and western blot were utilized to evaluate the regulatory relationship between Linc-00475 and p53.Results: High expression of Linc-00475 (P < 0.001) and low expression of p53 (P < 0.01) were associated with poor prognosis. There was a negative correlation between the expression of Linc-00475 and p53 in gastric cancer (Pearson's coefficient test, r = -0.405; P < 0.001). The co-expression of high-level Linc-00475 and low-level p53 can thus be used as an independent prognostic factor (P = 0.001). Linc-00475 was also shown to regulate aerobic glycolysis. Western blot and qRT-PCR demonstrated that Linc-00475 regulates the expression of p53.Conclusion: The co-expression of Linc-00475 and p53 can be used as a reference index for evaluating the prognosis of gastric cancer. Linc-00475 regulates p53, thereby affecting glycolysis.

Prader–Willi region non-protein coding RNA 1 suppressed gastric cancer growth as a competing endogenous RNA of miR-425-5p

2018 ◽  
Vol 132 (9) ◽  
pp. 1003-1019 ◽  
Author(s):  
Zihao Chen ◽  
Hongping Ju ◽  
Shan Yu ◽  
Ting Zhao ◽  
Xiaojie Jing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Western Blot ◽  
Microarray Analysis ◽  
Tumor Xenograft ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Protein Coding ◽  
Qrt Pcr ◽  
Rip Assay

Gastric cancer (GC) is one of the major global health problems, especially in Asia. Nowadays, long non-coding RNA (lncRNA) has gained significant attention in the current research climate such as carcinogenesis. This research desires to explore the mechanism of Prader–Willi region non-protein coding RNA 1 (PWRN1) on regulating GC process. Differentially expressed lncRNAs in GC tissues were screened out through microarray analysis. The RNA and protein expression level were detected by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, apoptosis rate, metastasis abilities were respectively determined by cell counting kit 8 (CCK8), flow cytometry, wound healing, and transwell assay. The luciferase reporter system was used to verify the targetting relationships between PWRN1, miR-425-5p, and phosphatase and tensin homolog (PTEN). RNA-binding protein immunoprecipitation (RIP) assay was performed to prove whether PWRN1 acted as a competitive endogenous RNA (ceRNA) of miR-425-5p. Tumor xenograft model and immunohistochemistry (IHC) were developed to study the influence of PWRN1 on tumor growth in vivo. Microarray analysis determined that PWRN1 was differently expressed between GC tissues and adjacent tissues. qRT-PCR revealed PWRN1 low expression in GC tissues and cells. Up-regulated PWRN1 could reduce proliferation and metastasis and increase apoptosis in GC cells, while miR-425-5p had reverse effects. The RIP assay indicated that PWRN1 may target an oncogene, miR-425-5p. The tumor xenograft assay found that up-regulated PWRN1 suppressed the tumor growth. The bioinformatics analysis, luciferase assay, and Western blot indicated that PWRN1 affected PTEN/Akt/MDM2/p53 axis via suppressing miR-425-5p. Our findings suggested that PWRN1 functioned as a ceRNA targetting miR-425-5p and suppressed GC development via p53 signaling pathway.

scholarly journals AKNA Is a Potential Prognostic Biomarker in Gastric Cancer and Function as a Tumor Suppressor by Modulating EMT-Related Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Gang Wang ◽  
Dan Sun ◽  
Wenhui Li ◽  
Yan Xin
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Western Blot ◽  
Signaling Pathway ◽  
Gene Set Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Potential Biomarker ◽  
Cell To Cell Adhesion

The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases’ data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.

scholarly journals Capicua homology protein inhibits the progression of gastric cancer through the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
LU GE ◽  
Chang-long Hu ◽  
Zheng-hui Ge ◽  
Chun-rong Wang ◽  
Li Qian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Qrt Pcr

Abstract Purpose Capicua homolog protein (CIC) played a broad role in the development of cancer in humans, however, its role in the progression of gastric cancer (GC) specifically has been unclear. This study aimed to explore the expression of CIC and its potential clinical value in patients with GC. Methods The CIC levels in GC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). And the in-vitro effects of CIC expression in MGC-803 cells on their proliferation, invasion, and the progression of epithelial-mesenchymal transition were assessed by CCK-8 assays, Matrigel-invasion analysis, qRT-PCR and Western blot assays, separately. In addition, the effects of downregulation of CIC on the activation of PI3K/AKT signaling pathway were measured using Western-blot analysis. Results The results showed CIC levels were lower in GC tissues and GC cell lines, and these lower CIC levels were correlated with tumor differentiation, Helicobacter pylori infection, TNM stage, and patient survival. In addition, CIC overexpression could promote cell proliferation, invasion, and progression of epithelial-mesenchymal transition in MGC-803 cells. Notably, exotic expression of CIC inactivated the phosphoinositide 3-kinase/protein kinase B signaling pathway. Conclusions In conclusion, our finding suggested CIC could serve as a potential diagnostic and prognostic biomarker and a probable therapy target for GC.

scholarly journals HOTAIR, HOXC13, and HOXC10 Are Overexpressed in Gastric Cancer

2021 ◽  
Author(s):  
Mahvash Habibi ◽  
Reza Fakhari ◽  
Mina Zamani ◽  
Hamid Galehdari
Keyword(s):  
Gastric Cancer ◽  
Significant Relationship ◽  
Perineural Invasion ◽  
Hox Genes ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Genes Expression ◽  
Carcinoma Metastasis ◽  
Positive Correlations

Abstract Gastric cancer is concerned as the second leading cause of tumor-associated death worldwide after lung tumors and is specified as one of the most common malignant cancers. Given the increasing importance of HOX genes in gastric cancer research, this study was aimed at exploring the expression profile of HOTAIR, HOXC13, HOXC10, HOXC13-AS, and HOXC‑AS3 in gastric cancer. To achieve this goal, 30 pairs of tumor and normal margin samples were assessed for these genes expression analyses via qRT-PCR. result we found that, the HOTAIR, HOXC13, and HOXC10 expression was significantly increased in cancer tissue samples in comparison with adjacent normal tissue samples, P<0.01. Moreover, there were significant positive correlations between the expressions of genes studied: HOXC‑AS3 and HOXC10 (r=0.52, P<0.003), HOXC13-AS and HOXC13 (r=0.57, P<0.001), HOTAIR and HOXC‑AS3 (r=0.39, P<0.03), HOTAIR and HOXC13-AS (r=0.36, P<0.05). The HOXC13 and HOXC10 expression exhibited a significant relationship with both distant metastasis and perineural invasion (metastasis: P<0.014, r=0.443 and P<0.0041, r=0.51 perineural invasion: P<0.025, r=0.41 and P<0.0017, r=0.55). The HOXC13-AS displayed a significant relationship with the sex factor so that in females the expression of this gene was higher than males (P<0.030, r=0.4). Our findings suggest that the expression of HOXC genes and HOTAIR lncRNA increased through gastric tumor progression and thus they possibly participate in malignant transformation and gastric carcinoma metastasis.

scholarly journals MicroRNA-99a promotes cell proliferation, migration and invasion in gastric cancer by modulating c-Src

2019 ◽  
Author(s):  
Yue Pan ◽  
Weixing Chen ◽  
Xin Yuan ◽  
Hongpeng Lu ◽  
Lei Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Normal Tissues ◽  
Qrt Pcr

Abstract Background: Recent studies have shown that microRNA-99a(miR-99a)plays a key role in the development of virious malignancies; however, its relationship with gastric cancer remains unclear. In this study, we investigated the functions and potential mechanisms of miR-99a in gastric cancer. Methods: Real-time qRT-PCR was used to assess the expression levels of miR-99a in gastric cancer tissue samples and cell lines compared to their matched adjacent normal tissues and a normal gastric mucosa epithelial cell line, respectively. SGC-7901 cells were transfected with miR-99a mimics and negative controls to determine the effects of miR-99a overexpression on cell proliferation, cell cycle transition, migration and invasion of gastric cancer cells in vitro . The role of miR-99a in endogenous c-Src expression in gastric cancer cells was also investigated by qRT-PCR and Western blotting. Results: Our results showed a significant increase in miR-99a expression in both gastric cancer tissues and cells compared to normal tissues and cells. Overexpression of miR-99a significantly promoted the cell proliferation, migration and invasion of gastric cancer cells compared to normal cells, with a concurrent increase in the S+G2 phases of the cell cycle. Further investigations found that miR-99a overexpression led to significant upregulation of endogenous c-Src. Conclusion: Taken together, our findings suggest that miR-99a may act as a tumour promoter in the pathogenesis of gastric cancer by indirectly modulating c-Src expression.

Effects of Bcl-2, Bax and P53 Gene Protein Expressions in Gastric Cancer Tissue on the Apoptosis of Cancer Cells

2013 ◽  
Vol 423-426 ◽  
pp. 358-361
Author(s):  
Lei Zhang ◽  
Da Peng Li ◽  
Guan Nan Lu
Keyword(s):  
Gastric Cancer ◽  
P53 Protein ◽  
P53 Gene ◽  
Gastric Cancer Tissue ◽  
Normal Lung ◽  
Cancer Tissue ◽  
P53 Expression ◽  
Bax Protein ◽  
Significant Difference ◽  
Positive Rate

Objective: To investigate the expression of p53 gene in gastric cancer tissue and its correlation with bcl-2 and bax protein expression in relationship and discuss the significance of their correlation in clinic. Methods: Pathological specimens from 100 gastric cancer patients with complete medical data and 24 normal lung tissue specimens were selected. Immunohistochemical streptavidin-biotin-peroxidase assay was used to detect the expression of bcl-2, bax and p53 protein. Results: p53 expression was positively correlated with bcl-2 expression (Pearson's R =0.491, P <0.05). The positive expression of p53 was no significantly correlated with bax expression (P> 0.05). The positive rate of p53 expression in the well-differentiated gastric cancer tissues was 17.6%, the positive rate in the differentiated tissues was 90.9%, the positive rate in the poorly differentiated tissues was 72.7%, and There was a significant difference in the expression of p53 in the three tissues (P <0.05). The expression of p53 in the TNM staging showed that the positive rate in stage Iand IIwas 27.3%, the positive rate in stage III and stage IVwas 89.3%, the difference between them was significant (P <0.05). Conclusions: The expression of p53 gene has an obvious clinical significance for the assessment of degree of malignancy and the prognosis of gastric cancer. Bcl-2 and p53 gene expression could jointly promote the development of gastric cancer in a synergistic way by acting on different stages of apoptosis, or bcl-2s participating in p53-induced mitochondria-mediated apoptosis signaling pathways.

Targeting the MALAT1-miR-206-GLS axis enhances the apoptotic effects of gastric cancer cells by mild hyperthermia treatments

2020 ◽  
Author(s):  
Huijuan Shi ◽  
Kejun Li ◽  
Jinxin Feng ◽  
Gaojie Liu ◽  
Yanlin Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Glutamine Metabolism ◽  
Cancer Tissue ◽  
Activity Detection ◽  
Hyperthermia Treatment ◽  
Mild Hyperthermia ◽  
Qrt Pcr ◽  
Short Time ◽  
Apoptotic Effects

Abstract Background: To explore the molecular mechanisms and modulatory effects of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the hyperthermia-induced gastric cancer cell death. Methods: Combined qRT-PCR and GLS activity detection of glutamine metabolism, we demonstrate the difference of expression of MALAT1 and miR-206 in normal or cancer tissue/ several cell lines and the roles of two in regulation of glutamine, respectively. The relation of MALAT1 and miR-206 was research by bioinformatical analysis and luciferase report. In addition, the molecular regulation between apoptotic effects and MALAT1-miR-206-GLS axis in gastric cancer after mild hyperthermia treatments were discovered by western blotting, luciferase report, quantitative real-time PCR (qRT-PCR), GLS activity detection of glutamine metabolism and cell viability test. Results: MALAT1 positively associated with GC by promoting glutamine metabolism under short time hyperthermia treatment, it involved in an adaptive reaction, an increased glutamine metabolism rate which could be further overridden by long time hyperthermia exposures. miR-206 could inhibit glutamine metabolism of GC and target 3’UTR of GLS which has oncogenic functions in GC directly. In addition, miR-206-suppresed glutamine metabolism was through direct targeting GLS. LncRNA MALAT1 inhibited miR-206 expression in GC by sponging it as a competing endogenous RNA. In summary, MALAT1-promoted glutamine metabolism was through the miR-206-GLS axis. Furthermore, we demonstrated effective approaches from the MALAT1-miR-206 axis for enhancing the mild hyperthermia-induced cancer death under a short time. Conclusions: Taken together, the MALAT1-miR-206-glutamine metabolism axis is a new strategy for enhancing the selectivity of hyperthermia treatments specific to GC cells

scholarly journals LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer Through MBNL1-AS1/ZFP36/CENPA Axis

2021 ◽  
Author(s):  
Yu Ding ◽  
Yingjie Li ◽  
Yunqiang Duan ◽  
Wan Wang ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Western Blot ◽  
Cancer Progression ◽  
Zinc Finger Protein ◽  
In Vivo Studies ◽  
Cancer Tissue ◽  
Western Blot Assay ◽  
Qrt Pcr

Abstract Background: Emerging studies suggested the notion that long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast cancer (BC).Methods: In the present research, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the Centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and Fluorescence in situ hybridization (FISH) were conducted to detect the mechanism.Results: The results revealed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. Conclusions: We elucidated a new mechanism for how MBNL1-AS1 regulated the phenotype of BC and targeting the MBNL1-AS1/ZFP36/CENPA axis might serve as therapeutic targets for BC patients.

scholarly journals Combinatorial Analysis of AT-Rich Interaction Domain 1A and CD47 in Gastric Cancer Patients Reveals Markers of Prognosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Qianfu Zhao ◽  
Qu Cai ◽  
Shanhe Yu ◽  
Jun Ji ◽  
Zhenggang Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cell Lines ◽  
Immune Cells ◽  
M2 Macrophages ◽  
Interaction Domain ◽  
Data Set ◽  
Qrt Pcr ◽  
Rich Interaction

Background: The AT-rich interaction domain 1A (ARID1A) is thought to be a tumor suppressive gene, and most of its mutations result in loss of expression of ARID1A protein. Combined with SIRPα on the surface of macrophages, CD47 on the surface of cancer cells can send an antiphagocytic “Don’t eat me” signal to the immune system that helps to avoid immune surveillance. However, the relationship between ARID1A and CD47 expression and their prognostic value in gastric cancer (GC) are still unknown.Methods: In this study, we evaluated ARID1A and CD47 expression in 154 GC patients’ tissues using tissue microarray. Expressions of ARID1A and CD47 in GC cell lines were determined by western blot and quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) techniques, and cell membranous CD47 expression was quantified by flow cytometry. In addition, chromatin immunoprecipitation (ChIP)–qPCR was used to determine the aspects of regulation of CD47 by ARID1A. The proportions of tumor-infiltrating immune cells were estimated on The Cancer Genome Atlas (TCGA) data set by using quanTIseq and EPIC algorithms. The infiltration of M1-polarized macrophages, M2-polarized macrophages, and regulatory T cells (Tregs) in GC tissues was determined by multispectral immunofluorescence.Results: A significant correlation was found between loss of ARID1A and high expression of CD47 at protein level in GC. By integrating 375 bulk RNA sequencing samples from TCGA data set, we found that mutated ARID1A correlated with high CD47 expression. In GC cell lines, knockdown of ARID1A significantly increased CD47 expression both at protein and mRNA levels as measured by western blot, qRT-PCR, and flow cytometry. Moreover, ChIP-qPCR revealed that CD47 was a direct downstream target gene of ARID1A in GC. Utilizing univariate and multivariate survival analyses, we found that patients with ARID1AlossCD47high expression had a worse prognosis. Estimation of infiltrating immune cells on TCGA data set showed that a higher infiltration proportion of M2 macrophages and Tregs was found in ARID1AmutatedCD47high expression subgroup. Furthermore, application of multispectral immunofluorescence revealed a higher infiltration proportion of M2 macrophages and Tregs in ARID1AlossCD47high GC tissues.Conclusion: Loss of ARID1A is strongly correlated with high CD47 expression in GC, and combination of ARID1A and CD47 is a promising prognosis factor in GC.

scholarly journals Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yangyang Wang ◽  
Shuchang Wang ◽  
Qin Yang ◽  
Jun Li ◽  
Fengrong Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Normal Tissue ◽  
Aerobic Glycolysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Degrading Enzymes ◽  
Pet Ct ◽  
Gastric Cancer Patients ◽  
Low Expression

Objective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric cancer patients in the future. Methods. Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results. The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions. Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy.

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