目的探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中Klotho(KL)基因的表达及其启动子区域甲基化水平与自噬基因LC3和RNA甲基转移酶基因NSUN2之间的关系。方法从癌症基因组图谱(The Cancer Genome Altas,TCGA)数...目的探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中Klotho(KL)基因的表达及其启动子区域甲基化水平与自噬基因LC3和RNA甲基转移酶基因NSUN2之间的关系。方法从癌症基因组图谱(The Cancer Genome Altas,TCGA)数据库中搜集有关HNSCC患者标准化的上四分位转录组测序(RNA-seq V2 RNA-seq by expectation maximization,RSEM)值和KL甲基化的β值(beta-value)信息,采用Kaplan-Meier生存曲线评估KL表达及其启动子区域甲基化与患者存活率之间的关系;采用Spearman相关检测分析KL的表达水平及其启动子区域甲基化水平与LC3和NSUN2表达之间的关系。结果在HNSCC患者当中,KL表达水平与患者的总生存期呈正相关,而KL启动子区域甲基化水平与总生存期间却有着相反的趋势。且KL高水平表达或其启动子区域低水平甲基化的HNSCC患者往往伴有LC3高表达和NSUN2低表达。结论在HNSCC患者中,KL表达水平及其启动子区域甲基化水平可作为提示患者预后的一种潜在的生物标志物,且其下游靶点LC3和NSUN2的表达也会受到KL表达的影响。展开更多
Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C depositio...Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C deposition is well characterized,other potential roles of NSUN2 in regulating viral replication remain largely unknown.In this study,the m5C modified residues catalyzed by NSUN2 on enterovirus 71(EV71)RNAs were mapped.NSUN2,along with m5C modifications,played multiple roles during the EV71 life cycle.Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs.Additionally,NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination.Furthermore,both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated.Taken together,this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication,and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.展开更多
RNA modifications affect many biological processes and physiological diseases.The 5-methylcytosine(m^(5)C)modification regulates the progression of multiple tumors.However,its characteristics and functions in hepatoce...RNA modifications affect many biological processes and physiological diseases.The 5-methylcytosine(m^(5)C)modification regulates the progression of multiple tumors.However,its characteristics and functions in hepatocellular carcinoma(HCC)remain largely unknown.Here,we found that HCC tissues had a higher m^(5)C methylation level than the adjacent normal tissues.Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways,such as the Ras and PI3K-Akt pathways.The m^(5)C methyltransferase NSUN2 was highly expressed in HCC tissues.Interestingly,the expression of many genes was positively correlated with the expression of NSUN2,including GRB2,RNF115,AATF,ADAM15,RTN3,and HDGF.Real-time PCR assays further revealed that the expression of the mRNAs of GRB2,RNF115,and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells.Furthermore,NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway.Moreover,knocking down NSUN2 caused cell cycle arrest.Taken together,our study demonstrates the vital role of NSUN2 in the progression of HCC.展开更多
文摘目的探究头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中Klotho(KL)基因的表达及其启动子区域甲基化水平与自噬基因LC3和RNA甲基转移酶基因NSUN2之间的关系。方法从癌症基因组图谱(The Cancer Genome Altas,TCGA)数据库中搜集有关HNSCC患者标准化的上四分位转录组测序(RNA-seq V2 RNA-seq by expectation maximization,RSEM)值和KL甲基化的β值(beta-value)信息,采用Kaplan-Meier生存曲线评估KL表达及其启动子区域甲基化与患者存活率之间的关系;采用Spearman相关检测分析KL的表达水平及其启动子区域甲基化水平与LC3和NSUN2表达之间的关系。结果在HNSCC患者当中,KL表达水平与患者的总生存期呈正相关,而KL启动子区域甲基化水平与总生存期间却有着相反的趋势。且KL高水平表达或其启动子区域低水平甲基化的HNSCC患者往往伴有LC3高表达和NSUN2低表达。结论在HNSCC患者中,KL表达水平及其启动子区域甲基化水平可作为提示患者预后的一种潜在的生物标志物,且其下游靶点LC3和NSUN2的表达也会受到KL表达的影响。
基金supported by the National Natural Science Foundation of China(31970168)the Key R&D Program of Hubei Province(2021BCD004)+2 种基金the Hubei Central Leading Local Science and Technology Special Project(2022BGE245)the Hubei Science and Technology Major Project[2021ACB004]the Wuhan Knowledge Innovation Special Project(2023020201020303).
文摘Increasing evidences suggest that the methyltransferase NSUN2 catalyzes 5-methylcytosine(m5C)modifications on viral RNAs,which are essential for the replication of various viruses.Despite the function of m5C deposition is well characterized,other potential roles of NSUN2 in regulating viral replication remain largely unknown.In this study,the m5C modified residues catalyzed by NSUN2 on enterovirus 71(EV71)RNAs were mapped.NSUN2,along with m5C modifications,played multiple roles during the EV71 life cycle.Functional m5C modified nucleotides increased the translational efficiency and stability of EV71 RNAs.Additionally,NSUN2 was found to target the viral protein VP1 for binding and promote its stability by inhibiting the ubiquitination.Furthermore,both viral replication and pathogenicity in mice were largely attenuated when functional m5C residues were mutated.Taken together,this study characterizes distinct pathways mediated by NSUN2 in regulating EV71 replication,and highlights the importance of its catalyzed m5C modifications on EV71 RNAs for the viral replication and pathogenicity.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32170594 and 31870809)the Province and Ministry Coconstruction Major Program of Medical Science and Technique Foundation of Henan Province(Grant No.SBGJ202001007)the Special Fund for Young and Middle School Leaders of Henan Health Commission(Grant No.HNSWJW-2020017),China.
文摘RNA modifications affect many biological processes and physiological diseases.The 5-methylcytosine(m^(5)C)modification regulates the progression of multiple tumors.However,its characteristics and functions in hepatocellular carcinoma(HCC)remain largely unknown.Here,we found that HCC tissues had a higher m^(5)C methylation level than the adjacent normal tissues.Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways,such as the Ras and PI3K-Akt pathways.The m^(5)C methyltransferase NSUN2 was highly expressed in HCC tissues.Interestingly,the expression of many genes was positively correlated with the expression of NSUN2,including GRB2,RNF115,AATF,ADAM15,RTN3,and HDGF.Real-time PCR assays further revealed that the expression of the mRNAs of GRB2,RNF115,and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells.Furthermore,NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway.Moreover,knocking down NSUN2 caused cell cycle arrest.Taken together,our study demonstrates the vital role of NSUN2 in the progression of HCC.
