Mutational landscape of TP53 and CDH1 in gastric cancer

In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 mutation.As a tumor suppressor gene,TP53 is implicated in more than half of all tumor occurrences.TP53 gene mutations in GC tissue may be related with clinical pathological aspects.The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy.CDH1 encodes E-cadherin,which is involved in cell-to-cell adhesion,epithelial structure maintenance,cell polarity,differentiation,and intracellular signaling pathway modulation.CDH1 mutations and functional loss can result in diffuse GC,and CDH1 mutations can serve as independent prognostic indicators for poor prognosis.GC patients can benefit from genetic counseling and testing for CDH1 mutations.Demethylation therapy may assist to postpone the onset and progression of GC.The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations,as well as providing some basis for evaluating the prognosis of GC patients.

DNA and histone methylation in gastric carcinogenesis

Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA,and these changes lead to transcriptional activation or silencing of the gene.Over the years,the study of epigenetic processes has increased,and novel therapeutic approaches that target DNA methylation and histone modifications have emerged.A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment.Here,we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome.

Regulation of demethylation and re-expression of RASSF1A gene in gastric cancer cell lines by combined treatment of 5-Aza-CdR and NaB

AIM： To investigate the changes of methylation state and expression of RASSF1A gene in human gastric cancer cell lines SGC7901 and BGC823 which were treated in vitro with demethlylating agent 5-Aza-CdR in combination with histone deacetylase inhibitor NaB. METHODS： After SGC7901 and BGC823 cells were treated with 5-Aza-CdR and/or NaB, the methylation state of RASSFIA gene was detected by methylationspecific PCR, and the changes in expression of mRNA and protein level of RASSFIA gene were observed by RT-PCR and Western-blotting before and after drug treatment. RESULTS： Hypermethylation was detected in the promoter region of RASSF1A gene in both SGC7901 and BGC823 cells, and there was no expression of this gene at both mRNA and protein level. After treatment with 5-Aza-CdR, demethylation occurred in the promoter region of RASSFIA gene, which subsequently induced re-expression of this gene. The treatment with NaB alone showed no effect on the methylation state and expression of RASSFIA gene. The combined treatment of 5-Aza-CdR and NaB induced complete demethylation of RASSFIA gene, leading to a significantly higher reexpression of the mRNA and protein of RASSFIA than those treated with 5-Aza-CdR alone （P 〈 0.05）. CONCLUSION： Hypermethylation in the promoter region is related to inactivation of RASSFIA gene in human gastric cancer cell lines SGC7901 and BGC823, while demethlylating agent 5-Aza-CdR can reverse the methylation state of RASSF1A gene and induce itsre-expression. Histone deacetylase inhibitor NaB had a synergistic effect with 5-Aza-CdR in both demethylation and gene transcriptional regulation.

DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus

Gastric cancer is a leading cause of cancer death worldwide,and significant effort has been focused on clarifying the pathology of gastric cancer.In particular,the development of genome-wide analysis tools has enabled the detection of genetic and epigenetic alterations in gastric cancer;for example,aberrant DNA methylation in gene promoter regions is thought to play a crucial role in gastric carcinogenesis.The etiological viewpoint is also essential for the study of gastric cancers,and two distinct pathogens,Helicobacter pylori(H.pylori)and Epstein-Barr virus(EBV),are known to participate in gastric carcinogenesis.Chronic inflammation of the gastric epithelium due to H.pylori infection induces aberrant polyclonal methylation that may lead to an increased risk of gastric cancer.In addition,EBV infection is known to cause extensive methylation,and EBV-positive gastric cancers display a high methylation epigenotype,in which aberrant methylation extends to not only Polycomb repressive complex(PRC)-target genes in embryonic stem cells but also non-PRC-target genes.Here,we review aberrant DNA methylation in gastric cancer and the association between methylation and infection with H.pylori and EBV.

PCR-SSCP-DNA sequencing method in detecting PTEN gene mutation and its signifi cance in human gastric cancer

AIM: To discuss the possible effect of PTEN gene mutations on occurrence and development of gastric cancer. METHODS: Fifty-three gastric cancer specimens were selected to probe PTEN gene mutations in genome of gastric cancer and paracancerous tissues using PCR-SSCP-DNA sequencing method based on microdissection and to observe the protein expression by immunohistochemistry technique. RESULTS: PCR-SSCP-DNA sequencing indicated that 4 kinds of mutation sites were found in 5 of 53 gastric cancer specimens. One kind of mutation was found in exons. AA-TCC mutation was located at 40bp upstream of 3’ lateral exon 7 (115946 AA-TCC). Such mutations led to terminator formation in the 297th codon of the PTEN gene. The other 3 kinds of mutation were found in introns,including a G-C point mutation at 91 bp upstream of 5’ lateral exon 5(90896 G-C),a T-G point mutation at 24 bp upstream of 5’ lateral exon 5 (90963 T-G),and a single base A mutation at 7 bp upstream of 5’ lateral exon 5 (90980 A del). The PTEN protein expression in gastric cancer and paracancerous tissues detected using immunohistochemistry technique indicated that the total positive rate of PTEN protein expression was 66% in gastric cancer tissue,which was significantly lower than that (100%) in paracancerous tissues (P < 0.005). CONCLUSION: PTEN gene mutation and expression may play an important role in the occurrence and development of gastric cancer.

Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines

AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification. METHODS： We used chromatin immunoprecipitation （CHIP） assay to assess the status of histone acetylation and methylation in promoter regions of the p16 and rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific PCR （MSP） to evaluate the effect of 5-Aza-2＇- deoxycytidine （5-Aza-dC）, trichostatin A （TSA） or their combination treatment on DNA methylation status. We used RT-PCR to determine whether alterations of histone modification status after 5-Aza-dC and TSA treatment are reflected in gene expression. RESULTS： For thep16 and MLH1 genes in two cell lines, silenced loci associated with DNA hypermethylation were characterized by histone H3-K9 hypoacetylation and hypermethylation and histone H3-K4 hypomethylation. Treatment with TSA resulted in moderately increased histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9 methylation and minimal effects on gene expression. In contrast, treatment with 5-Aza- dC rapidly reduced histone H3-K9 methylation at the silenced loci and resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and TSA was synergistic in reactivating gene expression at the loci showing DNA hypermethylation. Similarly, histone H3-K4 methylation was not affected alter TSA treatment, andincreased moderately at the silenced loci after 5-Aza-dC treatment. CONCLUSION： Hypermethylation of DNA in promoter CpG islands is related to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation in different regions of the promoters studied correlates with DNA methylation status of each gene in gastric cancer cells. However, histone H3-K9 acetylation and H3-K4 methylation inversely correlate with DNA methylation status of each gene in gastric cancer cells. Alteration of DNA methylation affects histone modification.

Metastatic suppressor genes inactivated by aberrant methylation in gastric cancer

AIM: To screen out the differentially methylated DNA sequences between gastric primary tumor and metastatic lymph nodes, test the methylation difference of gene PTPRG between primary gastric tumor and metastatic lymph nodes, and test the regulatory function of 5-aza- 2-deoxycytidine which is an agent with suppression on methylation and the level of methylation in gastric cancer cell line. METHODS: Methylated DNA sequences in genome were enriched with methylated CpG islands amplification (MCA) to undergo representational difference analysis (RDA), with MCA production of metastatic lymph nodes as tester and that of primary tumor as driver. The obtained differentially methylated fragments were cloned and sequenced to acquire the base sequence, which was analyzed with bioinformatics. With methylation-specific PCR (MSP) and RT-PCR, methylation difference of gene PTPRG was detected between primary tumor and metastatic lymph nodes in 36 cases of gastric cancer. Methylation of gene PTPRG and its regulated expression were observed in gastric cancer cell line before and after being treated with methylation-suppressive agent. RESULTS: Nineteen differentially methylated sequences were obtained and located at 5' end, exons, introns and 3' end, in which KL59 was observed to be located at 9p21 as the first exon of gene p16 and KL22 to be located at promoter region of PRPRG . KL22, as the probes, was hybridized with driver, tester and 3-round RDA products respectively with all positive signals except with the driver. Significant difference was observed in both methylation rate of gene PTPRG and PTPRG mRNA expression rate between primary tumor and metastatic lymph nodes. Demethylation of gene PTPRG, with recovered expression of PTPRG mRNA, was observed after gastric cancer cell line being treated with methylation-suppressive agent. CONCLUSION: Difference exists in DNA methylation between primary tumor and metastatic lymph nodes of gastric cancer, with MCA-RDA as one of the good analytical methods. Significant difference exists in methylation of gene PTPRG between primary tumor and metastatic lymph nodes of gastric cancer. Methylation level in gastric cancer cell line can be decreased by 5-aza-2'-deoxycytidine, which is the methylation- suppressive agent, with PTPRG expression being recovered.

MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation

BACKGROUND Ectopic expression of miRNAs promotes tumor development and progression.miRNA(miR)-320a is downregulated in many cancers,including gastric cancer(GC).However,the mechanism underlying its downregulation and the role of miR-320a in GC are unknown.AIM To determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms.METHODS Quantitative real-time polymerase chain reaction(PCR)was used to determine expression of miR-320a in GC cell lines and tissues.TargetScanHuman7.1,miRDB,and microRNA.org were used to predict the possible targets of miR-320a,and a dual luciferase assay was used to confirm the findings.Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3(PBX3)in GC cells and tissue samples.Cell Counting Kit-8 proliferation,Transwell,wound healing,and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells.Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands.5-Aza-2’-deoxycytidine(5-Aza-CdR)and trichostatin A(TSA)were used to treat GC cells.RESULTS miR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues.miR-320a overexpression suppressed GC cell proliferation,invasion and migration,and induced apoptosis.PBX3 was a target of miR-320a in GC.The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA.CONCLUSION miR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells,partly by targeting PBX3.DNA methylation is an important mechanism associated with low expression of miR-320a.

Silence of HIN-1 expression through methylation of its gene promoter in gastric cancer

AIM: To clarify the role of high in normal-1 (HIN-1) gene promoter methylation during gastric cancer development. METHODS: Gastric cancer cell lines and tissue specimens were analyzed for expression of HIN-1 mRNA and protein using the semi-quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The methylation of the HIN-1 gene promoter was detected in gastric carcinoma cells and tissues using methylation-specific polymerase chain reaction. The 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium cell viability assay and flow cytometry were used to assess the changes in behaviors of gastric cancer cells with or without 5-aza-2’-deoxycytidine treatment. RESULTS: HIN-1 was not expressed in 4 of 5 gastric cancer cell lines. The demethylation reagent 5-aza-2’-deoxycytidine was able to induce or upregulate HIN-1 expression in gastric cancer cell lines, which is associated with reduction of tumor cell viability. Furthermore, methylation of the HIN-1 gene promoter was shown in 57.8% (26/45) of the primary gastric cancer and 42.1% (17/38) of adjacent tissue samples, but was not shown in normal gastric mucosa (0/10). From the clinicopathological data of the patients, methylation of the HIN-1 gene promoter was found to be associated with tumor differentiation (P = 0.000). CONCLUSION: High methylation of HIN-1 gene promoter results in silence of HIN-1 expression in gastric cancer. 5-aza-2’-deoxycytidine reverses HIN-1 methylation and reduces viability of gastric cancer cells.

Methylation of the PCDH8 (Protocadherin-8) gene in gastric cancer

Objective: To investigate the methylation status of the PCDH8 (Protocadherin-8) gene in gastric cancer tissues and find out the relationship between methylation status of the PCDH8 and clinicopathological features in gastric cancer patients. Methods: We first investigated the methylation status of the PCDH8 (Protocadherin-8) gene in 65 gastric cancer and detected aberrant promoter methylation in gastric cancers; and then analyzed he relationship between methylation status of the PCDH8 and clinicopathological status with SPSS 13.0 software. Results: We first investigated the methylation status of the PCDH8 (Protocadherin-8) gene in 65 gastric cancer and detected aberrant promoter methylation in 36 of 65 (55.4%) gastric cancers. There was no significant difference in the distribution of patients with methylation or unmethylation of PCDH8 in terms of age, sex, tumor size, distant metastasis, or TNM stage. Methylation of PCDH8 was significantly correlated to negative pathological lymph node metastasis (P=0.038) and tumor differentiation (P=0.01). These two factors were proved to be of prognostic importance. Conclusion: Methylated PCDH8 seems to have a trend for worse prognosis in gastric cancer. However, a further large series of tumor samples and a longer follow-up period are required to elucidate its potential role.

Correction to"MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation"

We rechecked the original data of Figure 3,Part.B,and found that 0 h group in the BGC-823 cell wound scratch assay was misapplied.Therefore,we are writing to apply for the modification of Figure 3,Part.B.

Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis

Although thousands of DNA damaging events occur in each cell every day,efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes,it might increase the risk of cancer. In addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors,Helicobacter pylori(H. pylori) infection is considered the main driving factor to gastric cancer development. Thus,in this review,we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis.

DNA methylation drives a new path in gastric cancer early detection:Current impact and prospects

Gastric cancer(GC)is one of the most common and deadly cancers worldwide.Early detection offers the best chance for curative treatment and reducing its mortality.However,the optimal population-based early screening for GC remains unmet.Aberrant DNA methylation occurs in the early stage of GC,exhibiting cancer-specific genetic and epigenetic changes,and can be detected in the media such as blood,gastric juice,and feces,constituting a valuable biomarker for cancer early detection.Furthermore,DNA methylation is a stable epigenetic alteration,and many innovative methods have been developed to quantify it rapidly and accurately.Nonetheless,large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking,precluding their implementation in clinical practice.In conclusion,after a critical analysis of the recent existing literature,we summarized the evolving roles of DNA methylation during GC occurrence,expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC,and discussed its challenges and prospects in clinical applications.

Genomic and epigenomic heterogeneity in molecularsubtypes of gastric cancer

Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.

Identification of differentially expressed genes regulated by methylation in colon cancer based on bioinformatics analysis

BACKGROUND DNA methylation, acknowledged as a key modification in the field of epigenetics, regulates gene expression at the transcriptional level. Aberrant methylation in DNA regulatory regions could upregulate oncogenes and downregulate tumor suppressor genes without changing the sequences.However, studies of methylation in the control of gene expression are still inadequate. In the present research, we performed bioinformatics analysis to clarify the function of methylation and supply candidate methylation-related biomarkers and drivers for colon cancer.AIM To identify and analyze methylation-regulated differentially expressed genes(MeDEGs) in colon cancer by bioinformatics analysis.METHODS We downloaded RNA expression profiles, Illumina Human Methylation 450 K BeadChip data, and clinical data of colon cancer from The Cancer Genome Atlas project. MeDEGs were identified by analyzing the gene expression and methylation levels using the edgeR and limma package in R software. Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed in the DAVID database and KEGG Orthology-Based Annotation System 3.0, respectively. We then conducted Kaplan–Meier survival analysis to explore the relationship between methylation and expression and prognosis. Gene set enrichment analysis(GSEA) and investigation of protein-protein interactions(PPI) were performed to clarify the function of prognosis-related genes.RESULTS A total of 5 up-regulated and 81 down-regulated genes were identified asMeDEGs. GO and KEGG pathway analyses indicated that MeDEGs were enriched in multiple cancer-related terms. Furthermore, Kaplan–Meier survival analysis showed that the prognosis was negatively associated with the methylation status of glial cell-derived neurotrophic factor(GDNF) and reelin(RELN). In PPI networks, GDNF and RELN interact with neural cell adhesion molecule 1. Besides, GDNF can interact with GDNF family receptor alpha(GFRA1), GFRA2, GFRA3, and RET. RELN can interact with RAFAH1 B1,disabled homolog 1, very low-density lipoprotein receptor, lipoprotein receptorrelated protein 8, and NMDA 2 B. Based on GSEA, hypermethylation of GDNF and RELN were both significantly associated with pathways including "RNA degradation," "ribosome," "mismatch repair," "cell cycle" and "base excision repair."CONCLUSION Aberrant DNA methylation plays an important role in colon cancer progression.MeDEGs that are associated with the overall survival of patients may be potential targets in tumor diagnosis and treatment.

Epigenetics: An emerging player in gastric cancer

Cancers,like other diseases,arise from gene mutations and/or altered gene expression,which eventually cause dysregulation of numerous proteins and noncoding RNAs.Changes in gene expression,i.e.,upregulation of oncogenes and/or downregulation of tumor suppressor genes,can be generated not only by genetic and environmental factors but also by epigenetic factors,which are inheritable but nongenetic modifications of cellular chromosome components.Identification of the factors that contribute to individual cancers is a prerequisite to a full understanding of cancer mechanisms and the development of customized cancer therapies.The search for genetic and environmental factors has a long history in cancer research,but epigenetic factors only recently began to be associated with cancer formation,progression,and metastasis.Epigenetic alterations of chromatin include DNA methylation and histone modifications,which can affect gene-expression profiles.Recent studies have revealed diverse mechanisms by which chromatin modifiers,including writers,erasers and readers of the aforementioned modifications,contribute to the formation and progression of cancer.Furthermore,functional RNAs,such as microRNAs and long noncoding RNAs,have also been identified as key players in these processes.This review highlights recent findings concerning the epigenetic alterations associated with cancers,especially gastric cancer.

Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer

AIM: To elucidate the relationship between apoptotic protease activating factor-1 (Apaf-1) gene and gastric cancer. METHODS: Thirty-five postoperative cancer and adjacent normal tissue samples were collected in the present study. Expression of the Apaf-1 gene in these samples was analyzed by semi-quantitative RT-PCR. Loss of heterozygosity (LOH) was used to determine whether there was loss of Apaf-1 gene in domain of 12q22-23 in the samples. Promoter methylation of Apaf-1 gene in the samples was analyzed by methylation specific (MSP) PCR. RESULTS: The expression of Apaf-1 mRNA in gastric cancer tissue samples was 51%. The LOH frequency of D12S346, D12S1706, D12S327, D12S1657 and D12S393 was 33%, 8%, 58%, 12% and 42%, respectively. Fifty percent LOH was found at two sites and 17% LOH at three sites. Apaf-1 mRNA expression decreased significantly in 13 cases (rs = 0.487, P = 0.003). The rate of Apaf-1 promoter methylation was 49% in gastric cancer tissue samples and 23% in para-cancerous tissue samples. Promoter methylation occurred significantly in 16 of 18 gastric cancer tissue samples with decreased expression of Apaf-1 mRNA rs = 0.886, P = 10-6). CONCLUSION: The expression of Apaf-1 gene is low in gastric cancer tissues. Methylation of Apaf-1 gene promoter and LOH in domain of 12q22-23 are the main reasons for the expression and altered expression of Apaf-1 gene.

结直肠癌p53和DNA损伤调节基因1的表达及临床意义

目的 分析p53和DNA损伤调节基因1(p53 and DNA damage regulated gene 1,PDRG1)在结直肠癌中的表达及其临床意义。方法 检索癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中结直肠癌数据集,比较PDRG1 mRNA在结直肠癌组织和正常结直肠组织中的表达差异,分析其表达与临床病理特征及预后的关系。DNA甲基化交互可视化数据库(DNA methylation interactive visualization database,DNMIVD)分析PDRG1基因甲基化与m RNA表达水平的关系。另选取本院2019年2月至2020年5月存档的102例结直肠癌组织及其癌旁正常结直肠组织石蜡标本进行验证,采用免疫组织化学法检测PDRG1蛋白的表达。结果 TCGA数据库分析发现,PDRG1 mRNA在结直肠癌组织(n=284)中的表达较正常结直肠组织(n=41)增高(P<0.01),且结直肠癌PDRG1 mRNA表达与拷贝数变异呈正相关(n=273;r=0.792,P<0.01)。DNMIVD分析显示,PDRG1启动子甲基化β值与基因表达水平呈负相关(r=-0.34,P<0.01)。TCGA数据库分析显示,结直肠癌患者(n=273)PDRG1 mRNA表达在肿瘤位置、TNM分期及远处转移方面比较,差异均具有统计学意义(均P<0.05);对245例结直肠癌患者进行Kaplan-Meier生存分析发现,PDRG1 mRNA高表达患者(以中位数为分界值,大于中位数为高表达)无瘤生存期较短(P=0.019)。免疫组织化学检测显示,结直肠癌组织中PDRG1蛋白表达阳性率高于正常结直肠癌组织[87.3%(89/102) vs32.4%(33/102),P<0.01]。结论 PDRG1在结直肠癌中高表达,且与肿瘤位置、远处转移和无瘤生存期有关,可能成为结直肠癌潜在的生物标志物。

Connexin 32 and 43 promoter methylation in Helicobacter pylori-associated gastric tumorigenesis

AIM: To explore the mechanism of abnormal Connexin (Cx) 32 and Cx43 expression in the gastric mucosa after Helicobacter pylori (H. pylori) infection.

DNA methylation and microRNAs in cancer

DNA methylation is a type of epigenetic modification in the human genome,which means that gene expression is regulated without altering the DNA sequence.Methylation and the relationship between methylation and cancer have been the focus of molecular biology researches.Methylation represses gene expression and can influence embryogenesis and tumorigenesis.In different tissues and at different stages of life,the level of methylation of DNA varies,implying a fundamental but distinct role for methylation.When genes are repressed by abnormal methylation,the resulting effects can include instability of that gene and inactivation of a tumor suppressor gene.MicroRNAs have some aspects in common with this regulation of gene expression.Here we reviewed the influence of gene methylation on cancer and analyzed the methods used to profile methylation.We also assessed the correlation between methylation and other epigenetic modifications and microRNAs.About 55 845 research papers have been published about methylation,and one-fifth of these are about the appearance of methylation in cancer.We conclude that methylation does play a role in some cancer types.