scholarly journals Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation

2021 ◽  
Author(s):  
yinggang hua ◽  
yanling liu ◽  
long li ◽  
guoyan liu
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Promoter Region ◽  
Methylation Status ◽  
Diffuse Gastric Cancer ◽  
Normal Tissues ◽  
The Difference ◽  
Diffuse Type Gastric Cancer ◽  
Cancer Tissues ◽  
Erk Signal Pathway

Abstract Background P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, its DNA methylation status or even the corresponding regulatory mechanism remains unknown. Methods In this study, DNA methylation chip was used to profile the genome-wide DNA methylation level in gastric cancer tissues. Then validated by the bioinformatics analysis in the TCGA database, Immunohistochemistry staining data obtained from the HPA database to verify the difference in protein expression between normal tissues and tumor tissues . Results The promoter region of P2RY1 was found to be highly methylated with 4 hypermethylated sites (|Δβ value| >0.2) in diffuse gastric cancer and the expression level of P2RY1 is relatively low compared with non-cancerous tissues. We also showed that MRS2365, a selective agonist of the P2RY1 receptor, can induce phosphorylation of ERK1/2, inhibit cell proliferation/migration and induce apoptosis. Conclusion High DNA methylation in the promoter region of P2RY1 may have contributed to the reduced expression of P2RY1’s mRNA, which is likely responsible for the “aggressive” nature of the diffuse type gastric cancer.

scholarly journals Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation

2021 ◽  
Author(s):  
Yinggang Hua ◽  
Long Li ◽  
Liangliang Cai ◽  
Guoyan Liu
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Promoter Region ◽  
Methylation Status ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Receptor Activation ◽  
Diffuse Gastric Cancer ◽  
Gastric Cancer Cells

Abstract P2RY1 receptor is known to cause cancer by activating the ERK signal pathway, its DNA methylation status or even the corresponding regulatory mechanism remains unknown. In this study, DNA methylation chip was used to profile the genome-wide DNA methylation level in gastric cancer tissues. Proliferation and apoptosis of the SGC7901 gastric cancer cell line were determined after treatment with a selective P2RY1 receptor agonist, MRS2365. The promoter region of P2RY1 was found to be highly methylated with 4 hypermethylated sites (|Δβ value| >0.2) in diffuse gastric cancer and then were validated by bioinformatic analysis in TCGA database. Analysis of MRS2365-treated cells by annexin-V/PI staining and Caspase-3 activity assays indicated the induction of apoptosis in SGC7901 cells. P2RY1 receptor activation in human SGC7901 gastric cancer cells via the MRS2365 agonist induced apoptosis and reduced cell growth. High DNA methylation in the promoter region of P2RY1 may have contributed to the reduced expression of P2RY1’s mRNA, which is likely responsible for the “aggressive” nature of the diffuse type gastric cancer.

SUV39H1-Mediated DNMT1 is Participated in the Epigenetic Regulation of Smad3 in Cervical Cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Li Zhang ◽  
Sijuan Tian ◽  
Minyi Zhao ◽  
Ting Yang ◽  
Shimin Quan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Epigenetic Regulation ◽  
Promoter Region ◽  
Methylation Status ◽  
Regulation Mechanism ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Immune Factor ◽  
Cancer Tissues

Background: Smad3 is a pivotal intracellular mediator for participating in the activation of multiple immune signal pathway. Objective: The epigenetic regulation mechanism of the positive immune factor Smad3 in cervical cancer remains unknown. Therefore, the epigenetic regulation on Smad3 is investigated in this study. Methods: The methylation status of SMAD3 was detected by Methylation-specific PCR (MS-PCR) and Quantitative Methylation-specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of SUV39H1-DNMT1-Smad3 regulation was elucidated using cervical cancer cell lines containing siRNA or/and overexpression system. Confirmation of the regulation of DNMT1 by SUV39H1 used Chromatin immunoprecipitation-qPCR (ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t tests and one-way ANOVAs. Results: H3K9me3 protein which regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate its expression in cervical cancer cells, resulting in the reduce expression of the downstream target gene DNMT1. In addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The depletion of DNMT1 effectively restores the expression of Smad3 in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1-DNMT1 was found to correlate with Smad3 expression in accordance with the expression at the cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this hypermethylation inhibits the subsequent gene expression. Conclusion: These results indicate that SUV39H1-DNMT1 is a crucial Smad3 regulatory axis in cervical cancer. SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.

scholarly journals Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mai Mahmoud Shaker ◽  
Taghreed Abdelmoniem shalabi ◽  
Khalda said Amr
Keyword(s):  
Dna Methylation ◽  
Dna Sequences ◽  
Promoter Region ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Methylation Status ◽  
Control Group ◽  
Case Group ◽  
Methyl Radical ◽  
Fertile Women

Abstract Background DNA methylation is an epigenetic process for modifying transcription factors in various genes. Methylenetetrahydrofolate reductase (MTHFR) stimulates synthesis of methyl radical in the homocysteine cycle and delivers methyl groups needed in DNA methylation. Furthermore, numerous studies have linked gene polymorphisms of this enzyme with a larger risk of recurrent pregnancy loss (RPL), yet scarce information is available concerning the association between epigenetic deviations in this gene and RPL. Hypermethylation at precise DNA sequences can function as biomarkers for a diversity of diseases. We aimed by this study to evaluate the methylation status of the promoter region of MTHFR gene in women with RPL compared to healthy fertile women. It is a case–control study. Hundred RPL patients and hundred healthy fertile women with no history of RPL as controls were recruited. MTHFR C677T was assessed by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Quantitative evaluation of DNA methylation was performed by high-resolution melt analysis by real-time PCR. Results The median of percentage of MTHFR promoter methylation in RPL cases was 6.45 [0.74–100] vs. controls was 4.50 [0.60–91.7], P value < 0.001. In the case group, 57 hypermethylated and 43 normo-methylated among RPL patients vs. 40 hypermethylated and 60 normo-methylated among controls, P< 0.005. Frequency of T allele in C677T MTHFR gene among RPL patients was 29% vs. 23% among the control group; C allele vs. T allele: odds ratio (OR) = 1.367 (95% confidence interval (CI) 0.725–2.581). Conclusion Findings suggested a significant association between hypermethylation of the MTHFR promoter region in RPL patients compared to healthy fertile women.

CDH1 germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome

2021 ◽  
pp. jmedgenet-2021-108226
Author(s):  
Giovanni Corso ◽  
Francesca Magnoni ◽  
Giulia Massari ◽  
Cristina Maria Trovato ◽  
Alessandra Margherita De Scalzi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Healthy Subjects ◽  
Relevant Literature ◽  
Germline Mutations ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Missense Mutations ◽  
Healthy Individuals ◽  
Cancer Syndrome ◽  
The Difference

The objective of this study was to determining the frequency of different sub-types of pathogenic CDH1 germline mutations in healthy and asymptomatic individuals from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations. The collected variants were classified according to their subtype into the following classes: missense, non-sense, splicing, insertions and deletions. The χ2 test was used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was statistically significant. CDH1 genetic screening data were retrieved for 224 patients with GC and 289 healthy individuals. Among the subjects that had tested CDH1 positive, splicing mutations were found in 30.4% of the healthy individuals and in 15.2% of the patients with GC (p=0.0076). Missense mutations were also found to occur in healthy subjects with higher frequency (22.2%) than in GC-affected individuals (18.3%), but the difference was not significant in this case. In families meeting the clinical criteria for the HDGC syndrome, CDH1 splicing and missense germline mutations have been reported to occur with higher frequency in healthy subjects than in patients with cancer. This preliminary observation suggests that not all pathogenic CDH1 germline mutations confer the same risk of developing GC.

scholarly journals Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF

2021 ◽  
Author(s):  
Zahra Nouri Ghonbalani ◽  
Shiva Shahmohamadnejad ◽  
Parvin Pasalar ◽  
Ehsan Khalili
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Promoter Region ◽  
Hct116 Cell ◽  
Methylation Status ◽  
Expression Level ◽  
Cancer Tissue ◽  
Vegf Expression ◽  
Cancer Tissues

Abstract PurposeColorectal cancer (CRC) is the second leading cause of death from cancer in adults. Recent advances have shown that cancer cells can have some epigenetic changes involved in all stages of cancer. It has also been shown that miR-424 acts as gene expression regulators in many biological processes, including angiogenesis with mediators such as VEGF. In the current study, to identify the potential role of miR-424 in colorectal cancer progression, methylation status of miR-424 promoter region and its expression level have been evaluated. Besides, the correlation between VEGF level and miR-424 expression level has been assessed.MethodsMethylation status miR-424 promoter was assessed using methylation-specific polymerase chain reaction (MSP). The expression level of miR-424 in human colorectal cancer tissue was analyzed by quantitative PCR. HCT116 cell line was selected to evaluate the correlation between the miR-424 expression level and the promoter's methylation status. VEGF expression, one out of mir-424 targets involved in angiogenesis and cancer progression, was measured by western blot analysis in the pairs of cancer tissues and their adjacent tissues.ResultsOur results have revealed that the promoter region of miR-424 is methylated in cancer cells compared to normal cells, leading to down-regulation of miR-424 in the colorectal cancer tissues compared to the normal tissues. Also, we found that the expression protein's level of VEGF in the tumor cells increased compared with normal tissues.ConclusionThe present study suggests that hypermethylation downregulates miR-424. VEGF expression is upregulated with decreased miR-424 in colorectal cancer, which results in cancer progression.

EPCO-01. MOLECULAR PROFILING OF SPINAL CORD EPENDYMOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi1-vi1
Author(s):  
Erika Yamazawa ◽  
Shota Tanaka ◽  
Genta Nagae ◽  
Takayoshi Umeda ◽  
Taijun Hana ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Methylation ◽  
Methylation Status ◽  
Neurofibromatosis Type ◽  
Methylation Pattern ◽  
Who Grade ◽  
Spinal Ependymoma ◽  
Fresh Frozen ◽  
Spinal Cord Ependymoma ◽  
The Difference

Abstract BACKGROUND Ependymomas are currently classified into 9 subgroups by DNA methylation profiles. Although spinal cord ependymoma (SP-EPN) is distinct from other tumors, diversity within SP-EPN is still unclear. Here, we used transcriptomic and epigenomic profiles to investigate the diversity among Japanese SP-EPN cases. MATERIALS AND METHODS We analyzed 57 SP-EPN patients (32 males and 25 females, aged from 18 to 78 years, median: 52), including two cases of neurofibromatosis type 2, five cases of grade 3 (WHO grade). We obtained transcriptome (RNA-seq) and DNA methylation (Infinium Methylation EPIC array) data from fresh frozen specimens of SP-EPN resected at the University of Tokyo Hospital and our collaborative groups. RESULTS Three cases had a previous intracranial ependymoma operation. Hierarchical clustering of the DNA methylation data showed that these three cases of intracranial origin as a different cluster from spinal origin. The 45 grade 2 spinal ependymoma showed a relatively homogenous methylation pattern. However, the methylation status of HOX gene cluster regions is compatible with the segment of origin, which reflects the cells of origins are derived after the determination of segment identity. RNA sequencing of 57 cases revealed two subgroups within grade 2. Gene ontology analysis of differentially expressed genes suggested the difference in metabolic state such as rRNA translation and mitochondrial respiration between the two expression subgroups. CONCLUSION Epigenetic analysis indicated the accurate body segment origin of SP-EPN. We observed that metabolic states could divide grade 2 spinal cord ependymoma into 2 subgroups and will present the relationship to clinicopathological information.

scholarly journals The expression and clinical significance of PDCD4 and Her-2 in human gastric cancer

2019 ◽  
Vol 17 ◽  
pp. 205873921982823
Author(s):  
Yuelou Yang ◽  
Xiangjun Jiang ◽  
Dong Li ◽  
Feiyan Wang ◽  
Qun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Western Blot ◽  
Clinical Significance ◽  
Normal Mucosa ◽  
Normal Tissues ◽  
Positive Rate ◽  
Her 2 ◽  
Cancer Tissues ◽  
Pdcd4 Protein

To investigate the correlation and clinical significance between programmed cell death factor 4 (PDCD4) and epidermal growth factor receptor 2 (Her-2) expressions and clinicopathological parameters in patients with gastric cancer, a total of 65 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expressions were detected by SP immunohistochemical staining, and 50 cases of gastric cancer and the corresponding normal mucosa with PDCD4 and Her-2 protein expression quantities were detected by Western blot, in order to analyze the relationship between the positive expressions of PDCD4 and Her-2 protein and the clinicopathological features of patients with gastric cancer. The results showed that the positive rate of PDCD4 protein expression in gastric cancer tissues was 7.7%, which was significantly lower than that in the corresponding normal tissues, that is, 77.5% ( P < 0.05); the positive rate of Her-2 expression was 41.5%, which was significantly higher than that of the corresponding normal tissues, which is 2.5% ( P < 0.05). The Western blot test showed that the expression of PDCD4 protein in gastric cancer was 0.3105 ± 0.0073, which was significantly lower than that in the corresponding normal tissues, that is, 0.9428 ± 0.0127 ( P < 0.05); the expression level of Her-2 protein in gastric cancer tissues was 0.9428 ± 0.0127, which was significantly higher than that of the corresponding normal mucosa, which is 0.2054 ± 0.0264 ( P < 0.05). The positive expressions of PDCD4 (5/65) and Her-2 (27/65) were significantly correlated with the differentiation degrees and TNM stages of gastric cancer ( P < 0.05). However, no significant correlation can be observed from Table 2 ( P > 0.05), regarding sex, age, tumor size, and lymph node metastasis. Our research claimed that PDCD4 and Her-2 may play an important role in the invasion and metastasis of gastric cancer, which has a negative correlation with biological behaviors of gastric cancer. The low expression of PDCD4 and the high expression of Her-2 in gastric cancer may promote the occurrence and progression of cancer. The PDCD4 and Her-2 test can be used as an index to evaluate the malignant biological behaviors of gastric cancer and prognosis, and provide a theoretical basis for targeted therapy.

scholarly journals Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303381990112
Author(s):  
Kan-kan Yang ◽  
Hui-mian Xu ◽  
Jin-yu Huang ◽  
Yu-xuan Guo ◽  
Zhen-ning Wang
Keyword(s):  
Gastric Cancer ◽  
Tnm Stage ◽  
Gastric Cancer Cells ◽  
Hmg Box ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
The Difference ◽  
Cox Proportional Hazard Regression ◽  
Cancer Tissues ◽  
Clinicopathological Variables

Background: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. Methods: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. Results: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis ( P = .027) and TNM stage ( P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival ( P = .034). Conclusions: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.

scholarly journals Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

2018 ◽  
Vol 19 (8) ◽  
pp. 2424 ◽  
Author(s):  
Shamshul Ansari ◽  
Boldbaatar Gantuya ◽  
Vo Tuan ◽  
Yoshio Yamaoka
Keyword(s):  
Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Cell Integrity ◽  
Diffuse Type ◽  
Asian Countries ◽  
Contributing Factors ◽  
Incidence And Mortality ◽  
Genetic Abnormalities ◽  
H Pylori ◽  
Diffuse Type Gastric Cancer

Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.

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