The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV c...The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.展开更多
目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征...目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征进行统计学分析。运用基因富集分析软件GSEA对肝癌组织中与RBM45相关的基因进行KEGG信号通路富集分析。结果与癌旁组织相比,肝癌组织中RBM45表达明显升高(P<0.001),且RBM45表达水平与患者临床分期、肿瘤分级及预后均显著相关(P<0.05),通过构建单变量和多变量COX风险回归模型分析RBM45表达与临床资料的相关性,结果表明RBM45可做为肝癌患者独立预后的危险因素(HR:2.75695%CI:1.785-4.255,P=4.813e-06);KEGG富集分析显示,RBM45可能与细胞周期、卵母细胞减数分裂、泛素介导的蛋白水解等信号通路密切相关。结论RBM45在肝癌组织中高表达,且其高表达的患者预后较差;RBM45表达可作为肝癌患者预后判断的独立标志物。展开更多
Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
目的探究m6A甲基化甲基转移酶RNA结合蛋白15(RNA-binding Motif Protein 15,RBM15)与宫颈癌的相关性及临床意义。方法选取2011年1月1日至2018年1月1日期间于皖南医学院第一附属医院进行诊治的宫颈癌病例132例,另选20例正常宫颈组织病例...目的探究m6A甲基化甲基转移酶RNA结合蛋白15(RNA-binding Motif Protein 15,RBM15)与宫颈癌的相关性及临床意义。方法选取2011年1月1日至2018年1月1日期间于皖南医学院第一附属医院进行诊治的宫颈癌病例132例,另选20例正常宫颈组织病例作为对照,共152例,通过免疫组化法检测RBM15在宫颈癌中和正常宫颈中的表达水平,分析其相关性,并研究其表达量与临床分期及临床病理特征之间的关系。结果RBM15在宫颈癌中的阳性表达率56%显著高于正常宫颈0%(P=0.001),且宫颈癌的期别越高,RBM15表达越强(P=0.002)。复发宫颈癌中RBM15的表达也呈现为随期别逐渐上升的趋势(P=0.156)。RBM15的阳性表达与宫颈癌的肿瘤最大径、淋巴结转移、神经侵犯、脉管癌栓有关(P<0.05),而与肿瘤分级、病理类型、发病年龄、鳞状上皮细胞癌抗原(Squamous cell carcinoma antigen,SCCA)无关(P>0.05)。结论RBM15在宫颈癌中呈高表达,且与宫颈癌分期及临床病理特征具有一定的相关性,RBM15表达升高也会造成宫颈癌患者预后不良,这一发现日后有望成为宫颈癌诊治的新靶点。展开更多
Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of ID...Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.展开更多
基金supported by the National Key R&D Program of China(No.2022YFA1303600 and No.2023YFC2306800)the National Natural Science Foundation of China(No.82372235 and No.82272315)the Sanming Project of Medicine in Shenzhen(No.SZSM202311032).
文摘The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.
文摘目的探讨核糖核酸结合基序蛋白45(RNA-binding motif protein 45,RBM45)在肝癌中的表达及其临床应用价值。方法应用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析RNA结合蛋白RBM45在肝癌中的表达,并关联临床资料及病理特征进行统计学分析。运用基因富集分析软件GSEA对肝癌组织中与RBM45相关的基因进行KEGG信号通路富集分析。结果与癌旁组织相比,肝癌组织中RBM45表达明显升高(P<0.001),且RBM45表达水平与患者临床分期、肿瘤分级及预后均显著相关(P<0.05),通过构建单变量和多变量COX风险回归模型分析RBM45表达与临床资料的相关性,结果表明RBM45可做为肝癌患者独立预后的危险因素(HR:2.75695%CI:1.785-4.255,P=4.813e-06);KEGG富集分析显示,RBM45可能与细胞周期、卵母细胞减数分裂、泛素介导的蛋白水解等信号通路密切相关。结论RBM45在肝癌组织中高表达,且其高表达的患者预后较差;RBM45表达可作为肝癌患者预后判断的独立标志物。
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
基金supported by the National Natural Science Foundation of China(Grant Nos.81572556 and 81402139).
文摘Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
