BACKGROUND In recent years,the prevalence of Alzheimer’s disease(AD)has increased,which places a great burden on society and families and creates considerable challenges for medical services.N6-methyladenine(m6A)deox...BACKGROUND In recent years,the prevalence of Alzheimer’s disease(AD)has increased,which places a great burden on society and families and creates considerable challenges for medical services.N6-methyladenine(m6A)deoxyribonucleic acid(DNA)adenine methylation is a novel biomarker and is abundant in the brain,but less common in AD.We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls(NCs)in China.AIM To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.METHODS A total of 179 AD patients(mean age 71.60±9.89 years;males:91;females:88)and 147 NCs(mean age 69.59±11.22 years;males:77;females:70)who were age-and sex-matched were included in our study.All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination.Apolipoprotein E(APOE)genotypes were measured through agarose gel electrophoresis.Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit(colorimetric).Global m6A levels in total DNA from ten AD patients with 18F-AV-45(florbetapir)positron emission tomography(PET)positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.RESULTS Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs(P=0.002;<0.05).And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting.There were significant differences between the two groups,which indicated that the leukocyte m6A DNA levels were different(P=0.005;<0.05).The m6A level was approximately 8.33%lower in AD patients than in NCs(mean 0.011±0.006 vs 0.012±0.005).A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population(r=0.143,P=0.01;<0.05).However,no relationship was found with APOEε4(P=0.633,>0.05).Further studies should be performed to validate these findings.CONCLUSION Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33%in China.展开更多
BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 p...BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.展开更多
目的:探究膀胱癌中N6-甲基腺苷(N6-methyladenosine,m6A)相关长非编码RNA(long non-coding RNA,lncRNA)及其与患者预后的关系。方法:通过癌症基因组图谱(the cancer genome Atlas,TCGA)数据库获取转录、突变和临床数据,获得m6A相关的lnc...目的:探究膀胱癌中N6-甲基腺苷(N6-methyladenosine,m6A)相关长非编码RNA(long non-coding RNA,lncRNA)及其与患者预后的关系。方法:通过癌症基因组图谱(the cancer genome Atlas,TCGA)数据库获取转录、突变和临床数据,获得m6A相关的lncRNA表达数据,采用共表达网络分析、Cox回归分析和最小绝对收缩和选择算法(least absolute shrinkage and se-lection operator,LASSO)回归分析鉴定与m6A相关的lncRNA,并构建风险预后模型和对其进行验证。然后,本研究还构建了列线图来预测膀胱癌患者的预后。通过基因本体(gene ontology,GO)、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)研究生物学功能的差异。使用ESTIMATE算法计算基质、免疫评分。采用单样本基因集富集分析(single sample gene set enrichment analysis,ssGSEA)算法定量分析免疫细胞浸润和免疫功能。采用oncoPredict算法预测潜在治疗药物。结果:本课题组确定了1739个m6A相关lncRNA,其中14个与预后相关。再通过LASSO回归分析筛选了5个m6A相关的lncRNA(GRK5-IT1、AC008883.2、AC145207.5、AC103746.1、AC104564.3)来构建预后预测模型。Kaplan-Meier和受试者工作特征曲线(receiver operating characteristic,ROC)曲线显示,该特征在训练集、验证集和全集中具有良好的预测能力。与其他临床特征相比,m6A相关lncRNA模型具有更高的诊断效率。免疫细胞浸润和ssGSEA分析进一步证实,特征lncRNA与膀胱癌患者的免疫状态显著相关。此外,高风险组对多种药物的治疗反应与低风险组存在显著差异。结论:5个m6A相关的特征ln-cRNA可能有助于评估膀胱癌患者的预后和免疫特征,并指导个性化治疗方案的制定。展开更多
基金Supported by the National Key R&D Program of China,No.2016YFC1306300and the National Natural Science Foundation of China,No.81974220.
文摘BACKGROUND In recent years,the prevalence of Alzheimer’s disease(AD)has increased,which places a great burden on society and families and creates considerable challenges for medical services.N6-methyladenine(m6A)deoxyribonucleic acid(DNA)adenine methylation is a novel biomarker and is abundant in the brain,but less common in AD.We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls(NCs)in China.AIM To analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.METHODS A total of 179 AD patients(mean age 71.60±9.89 years;males:91;females:88)and 147 NCs(mean age 69.59±11.22 years;males:77;females:70)who were age-and sex-matched were included in our study.All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination.Apolipoprotein E(APOE)genotypes were measured through agarose gel electrophoresis.Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit(colorimetric).Global m6A levels in total DNA from ten AD patients with 18F-AV-45(florbetapir)positron emission tomography(PET)positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.RESULTS Our ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs(P=0.002;<0.05).And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting.There were significant differences between the two groups,which indicated that the leukocyte m6A DNA levels were different(P=0.005;<0.05).The m6A level was approximately 8.33%lower in AD patients than in NCs(mean 0.011±0.006 vs 0.012±0.005).A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population(r=0.143,P=0.01;<0.05).However,no relationship was found with APOEε4(P=0.633,>0.05).Further studies should be performed to validate these findings.CONCLUSION Our results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33%in China.
基金Natural Science Foundation of Shandong Province,No.ZR2020MH207 and No.ZR2020MH251.
文摘BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.
文摘目的:探究膀胱癌中N6-甲基腺苷(N6-methyladenosine,m6A)相关长非编码RNA(long non-coding RNA,lncRNA)及其与患者预后的关系。方法:通过癌症基因组图谱(the cancer genome Atlas,TCGA)数据库获取转录、突变和临床数据,获得m6A相关的lncRNA表达数据,采用共表达网络分析、Cox回归分析和最小绝对收缩和选择算法(least absolute shrinkage and se-lection operator,LASSO)回归分析鉴定与m6A相关的lncRNA,并构建风险预后模型和对其进行验证。然后,本研究还构建了列线图来预测膀胱癌患者的预后。通过基因本体(gene ontology,GO)、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)研究生物学功能的差异。使用ESTIMATE算法计算基质、免疫评分。采用单样本基因集富集分析(single sample gene set enrichment analysis,ssGSEA)算法定量分析免疫细胞浸润和免疫功能。采用oncoPredict算法预测潜在治疗药物。结果:本课题组确定了1739个m6A相关lncRNA,其中14个与预后相关。再通过LASSO回归分析筛选了5个m6A相关的lncRNA(GRK5-IT1、AC008883.2、AC145207.5、AC103746.1、AC104564.3)来构建预后预测模型。Kaplan-Meier和受试者工作特征曲线(receiver operating characteristic,ROC)曲线显示,该特征在训练集、验证集和全集中具有良好的预测能力。与其他临床特征相比,m6A相关lncRNA模型具有更高的诊断效率。免疫细胞浸润和ssGSEA分析进一步证实,特征lncRNA与膀胱癌患者的免疫状态显著相关。此外,高风险组对多种药物的治疗反应与低风险组存在显著差异。结论:5个m6A相关的特征ln-cRNA可能有助于评估膀胱癌患者的预后和免疫特征,并指导个性化治疗方案的制定。
