目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p...目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p Background: The role of m6A methylation genes in the differentiation of colorectal cancer is currently unclear. This study combines bioinformatics analysis and experimental validation to explore the expression patterns of these genes in colorectal cancer and their potential mechanisms. Methods: Using bioinformatics, we found that YTHDF1, YTHDF2, ALKBH5, and WTAP are significantly aberrantly expressed in colorectal cancer (p < 0.05). In a real-world cohort from Lishui, quantitative PCR (qPCR) was used to measure mRNA expression of these four genes in CRC tissues and adjacent normal tissues. Multivariable logistic regression analysis with SPSS identified YTHDF1 and WTAP mRNA expression levels as being associated with CRC differentiation. Immunohistochemistry (IHC) was performed to examine corresponding protein levels, quantified using ImageJ. Results showed that YTHDF1 protein expression negatively correlated with CRC differentiation, whereas WTAP protein expression positively correlated. Additionally, multivariable Cox regression analysis was conducted to identify potential factors influencing CRC development. Results: In Lishui, YTHDF1 protein expression was negatively associated with CRC differentiation, while WTAP protein expression was positively associated. Age and alcohol consumption were key risk factors for CRC development, while no significant associations were found with sex or smoking. GO enrichment analysis suggests that YTHDF1 and WTAP may regulate the differentiation process of colorectal cancer by participating in mechanisms such as mRNA modification, translation regulation, and RNA stability. For the poorly differentiated CRC group, time to progression rate (TTP) was 100% and overall survival rate (OS) was 0% within three years. Conclusions: In Lishui City, the YTHDF1 and WTAP genes influence the differentiation of colorectal cancer and may serve as important therapeutic targets and biomarkers for the diagnosis of patients with colorectal cancer.展开更多
Background:RNA N6-methyladenosine(m6A)regulators are essential for numerous biological processes and are implicated in various diseases.However,the comprehensive role of m6A regulators in the context of liver transpla...Background:RNA N6-methyladenosine(m6A)regulators are essential for numerous biological processes and are implicated in various diseases.However,the comprehensive role of m6A regulators in the context of liver transplantation(LT)remains poorly understood.This study aimed to illustrate the relationship between m6A regulators and ischemia-reperfusion injury(IRI)following LT.Methods:Datasets were acquired from the Gene Expression Omnibus database.Differential analysis of the merged data identified the differentially expressed m6A regulators.Random forest(RF)models and nomograms were used to forecast the incidence and assess the IRI risk following LT.m6A regulators were classified into distinct subgroups using cluster analysis.The differential gene expression was validated using immunohistochemistry,immunofluorescence,and Western blotting.Results:We found significant disparities in the gene expression levels of the three m6A regulators between patients with and without LT.Wilms’tumor 1-associating protein(WTAP)expression was upregulated following LT.The RF models exhibited a high degree of accuracy in predicting IRI risk.Immune infiltration analysis showed that WTAP was an immune-associated m6A regulator that was closely associated with T and B cells.WTAP expression in the rat LT model was upregulated after 24 h of reperfusion,which was consistent with the results of the bioinformatics analysis.Conclusions:WTAP has a high diagnostic value for IRI in LT and influences the immune status of patients.Hence,WTAP,as a significant regulator of m6A,is a potential biomarker for the detection and implementation of immunotherapy for IRI following LT.展开更多
N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA中最普遍的一种修饰。Wilms肿瘤蛋白1相关蛋白(Wilms'tumor 1-associating protein,WTAP)作为m6A甲基化转移酶的调控亚基,与甲基转移样蛋白3(methyltransferase-like protei...N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA中最普遍的一种修饰。Wilms肿瘤蛋白1相关蛋白(Wilms'tumor 1-associating protein,WTAP)作为m6A甲基化转移酶的调控亚基,与甲基转移样蛋白3(methyltransferase-like protein 3,METTL3)、甲基转移样蛋白14(methyltransferase-like protein 14,METTL14)组成WMM复合物,催化m6A的产生。大量证据表明,WTAP可以通过调控RNA代谢,影响肿瘤的发生和进展,并与肿瘤的预后有着显著的相关性。本篇综述将关注WTAP的生物学功能和肿瘤中的作用,以及其作为肿瘤治疗潜在靶点的可行性。展开更多
N^(6)-methyladenosine(m^(6)A)modification,which is achieved by the METTL3/METTL14/WTAP methyltransferase complex,is the most abundant internal mRNA modification.Although recent evidence indicates that m^(6)A can regul...N^(6)-methyladenosine(m^(6)A)modification,which is achieved by the METTL3/METTL14/WTAP methyltransferase complex,is the most abundant internal mRNA modification.Although recent evidence indicates that m^(6)A can regulate neurodevelopment as well as synaptic function,the roles of m^(6)A modification in the cerebellum and related synaptic connections are not well established.Here,we report that Purkinje cell(PC)-specific WTAP knockout mice display early-onset ataxia concomitant with cerebellar atrophy due to extensive PC degeneration and apoptotic cell death.Loss of Wtap also causes the aberrant degradation of multiple PC synapses.WTAP depletion leads to decreased expression levels of METTL3/14 and reduced m^(6)A methylation in PCs.Moreover,the expression of GFAP and NF-L in the degenerating cerebellum is increased,suggesting severe neuronal injuries.In conclusion,this study demonstrates the critical role of WTAP-mediated m^(6)A modification in cerebellar PCs,thus providing unique insights related to neurodegenerative disorders.展开更多
To the Editor:Hepatocellular carcinoma(HCC)is a prominent contributor to cancer-related mortality on a global scale.While therapeutic approaches,such as surgical resection,liver transplantation,and radiofrequency abla...To the Editor:Hepatocellular carcinoma(HCC)is a prominent contributor to cancer-related mortality on a global scale.While therapeutic approaches,such as surgical resection,liver transplantation,and radiofrequency ablation,have demonstrated effectiveness for specific patient populations,the 5-year overall survival(OS)rate in HCC is discouragingly low,estimated at only 18%.This unfavorable outcome can primarily be attributed to the high recurrence and metastasis rates.[1]Therefore,there is an urgent need for novel therapeutic strategies or targets to surmount the challenges in treating HCC.展开更多
文摘目的:目前尚不清楚m6A甲基化基因在结直肠癌分化中的作用。本研究结合生物信息学分析与实验验证,探讨这些基因在结直肠癌中的表达特征及其潜在机制。方法:利用生物信息学,我们发现YTHDF1、YTHDF2、ALKBH5、WTAP与结直肠癌表达异常显著(p Background: The role of m6A methylation genes in the differentiation of colorectal cancer is currently unclear. This study combines bioinformatics analysis and experimental validation to explore the expression patterns of these genes in colorectal cancer and their potential mechanisms. Methods: Using bioinformatics, we found that YTHDF1, YTHDF2, ALKBH5, and WTAP are significantly aberrantly expressed in colorectal cancer (p < 0.05). In a real-world cohort from Lishui, quantitative PCR (qPCR) was used to measure mRNA expression of these four genes in CRC tissues and adjacent normal tissues. Multivariable logistic regression analysis with SPSS identified YTHDF1 and WTAP mRNA expression levels as being associated with CRC differentiation. Immunohistochemistry (IHC) was performed to examine corresponding protein levels, quantified using ImageJ. Results showed that YTHDF1 protein expression negatively correlated with CRC differentiation, whereas WTAP protein expression positively correlated. Additionally, multivariable Cox regression analysis was conducted to identify potential factors influencing CRC development. Results: In Lishui, YTHDF1 protein expression was negatively associated with CRC differentiation, while WTAP protein expression was positively associated. Age and alcohol consumption were key risk factors for CRC development, while no significant associations were found with sex or smoking. GO enrichment analysis suggests that YTHDF1 and WTAP may regulate the differentiation process of colorectal cancer by participating in mechanisms such as mRNA modification, translation regulation, and RNA stability. For the poorly differentiated CRC group, time to progression rate (TTP) was 100% and overall survival rate (OS) was 0% within three years. Conclusions: In Lishui City, the YTHDF1 and WTAP genes influence the differentiation of colorectal cancer and may serve as important therapeutic targets and biomarkers for the diagnosis of patients with colorectal cancer.
基金supported by grants from Chongqing Re-search Performance Incentive and Guidance Project(No.cstc2022jxjl120032)Chongqing Technology Innovation and Application Development(Key Project,No.cstc2021jscx-gksb X0060)。
文摘Background:RNA N6-methyladenosine(m6A)regulators are essential for numerous biological processes and are implicated in various diseases.However,the comprehensive role of m6A regulators in the context of liver transplantation(LT)remains poorly understood.This study aimed to illustrate the relationship between m6A regulators and ischemia-reperfusion injury(IRI)following LT.Methods:Datasets were acquired from the Gene Expression Omnibus database.Differential analysis of the merged data identified the differentially expressed m6A regulators.Random forest(RF)models and nomograms were used to forecast the incidence and assess the IRI risk following LT.m6A regulators were classified into distinct subgroups using cluster analysis.The differential gene expression was validated using immunohistochemistry,immunofluorescence,and Western blotting.Results:We found significant disparities in the gene expression levels of the three m6A regulators between patients with and without LT.Wilms’tumor 1-associating protein(WTAP)expression was upregulated following LT.The RF models exhibited a high degree of accuracy in predicting IRI risk.Immune infiltration analysis showed that WTAP was an immune-associated m6A regulator that was closely associated with T and B cells.WTAP expression in the rat LT model was upregulated after 24 h of reperfusion,which was consistent with the results of the bioinformatics analysis.Conclusions:WTAP has a high diagnostic value for IRI in LT and influences the immune status of patients.Hence,WTAP,as a significant regulator of m6A,is a potential biomarker for the detection and implementation of immunotherapy for IRI following LT.
文摘N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物信使RNA中最普遍的一种修饰。Wilms肿瘤蛋白1相关蛋白(Wilms'tumor 1-associating protein,WTAP)作为m6A甲基化转移酶的调控亚基,与甲基转移样蛋白3(methyltransferase-like protein 3,METTL3)、甲基转移样蛋白14(methyltransferase-like protein 14,METTL14)组成WMM复合物,催化m6A的产生。大量证据表明,WTAP可以通过调控RNA代谢,影响肿瘤的发生和进展,并与肿瘤的预后有着显著的相关性。本篇综述将关注WTAP的生物学功能和肿瘤中的作用,以及其作为肿瘤治疗潜在靶点的可行性。
基金supported by the National Natural Science Foundation of China(82121003,81970841,and 81790643)the Department of Science and Technology of Sichuan Province(2021YFS0386,2021YFS0369,20ZYD038,20ZYD037,2020JDZH0026,2021JDZH0022)+2 种基金the CAMS Innovation Fund for Medical Sciences(2019-12M-5-032)Huanhua Distingished Scholar grantthe Department of Chengdu Science and Technology(2021-YF05-01316-SN)。
文摘N^(6)-methyladenosine(m^(6)A)modification,which is achieved by the METTL3/METTL14/WTAP methyltransferase complex,is the most abundant internal mRNA modification.Although recent evidence indicates that m^(6)A can regulate neurodevelopment as well as synaptic function,the roles of m^(6)A modification in the cerebellum and related synaptic connections are not well established.Here,we report that Purkinje cell(PC)-specific WTAP knockout mice display early-onset ataxia concomitant with cerebellar atrophy due to extensive PC degeneration and apoptotic cell death.Loss of Wtap also causes the aberrant degradation of multiple PC synapses.WTAP depletion leads to decreased expression levels of METTL3/14 and reduced m^(6)A methylation in PCs.Moreover,the expression of GFAP and NF-L in the degenerating cerebellum is increased,suggesting severe neuronal injuries.In conclusion,this study demonstrates the critical role of WTAP-mediated m^(6)A modification in cerebellar PCs,thus providing unique insights related to neurodegenerative disorders.
基金supported by grants from the Capital’s Funds for Health Improvement and Research(No.2022-25121).
文摘To the Editor:Hepatocellular carcinoma(HCC)is a prominent contributor to cancer-related mortality on a global scale.While therapeutic approaches,such as surgical resection,liver transplantation,and radiofrequency ablation,have demonstrated effectiveness for specific patient populations,the 5-year overall survival(OS)rate in HCC is discouragingly low,estimated at only 18%.This unfavorable outcome can primarily be attributed to the high recurrence and metastasis rates.[1]Therefore,there is an urgent need for novel therapeutic strategies or targets to surmount the challenges in treating HCC.
