Objective Cytokine responses to activation of innate immunity differ between individuals,yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypot...Objective Cytokine responses to activation of innate immunity differ between individuals,yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic non-coding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.展开更多
Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remai...Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.展开更多
目的·研究胃癌组织细胞中长链非编码RNA(long-chain non-coding RNA,lncRNA)lincRNA-BBOX1-2的表达对于胃癌诊断及预后判断的价值。方法·实时定量PCR检测45例胃癌组织及癌旁正常组织中lincRNA-BBOX1-2的表达水平,分析lincRNAB...目的·研究胃癌组织细胞中长链非编码RNA(long-chain non-coding RNA,lncRNA)lincRNA-BBOX1-2的表达对于胃癌诊断及预后判断的价值。方法·实时定量PCR检测45例胃癌组织及癌旁正常组织中lincRNA-BBOX1-2的表达水平,分析lincRNABBOX1-2的表达水平与胃癌患者临床病理特征及预后的关系。结果·胃癌组织中lincRNA-BBOX1-2的表达水平高于癌旁正常组织(3.291±0.274 vs 1.125±0.075,P=0.000);胃癌组织中lincRNA-BBOX1-2的表达水平与肿瘤有/无淋巴结转移(P=0.005,r=0.172)及TNM分期(P=0.013,r=0.137)呈正相关。受试者工作特征曲线分析结果显示:lincRNA-BBOX1-2在预测胃癌发生时,其曲线下面积(area under the curve,AUC)值为0.916(95%CI 0.859~0.972);lincRNA-BBOX1-2在预测胃癌有/无淋巴结转移时,其AUC值为0.720(95%CI 0.565~0.875)。结论·胃癌组织中lincRNA-BBOX1-2的表达水平上调与胃癌的临床病理特征密切相关。lincRNA-BBOX1-2可能成为一个新的胃癌诊断分子标志物。展开更多
文摘Objective Cytokine responses to activation of innate immunity differ between individuals,yet the genomic and tissue-specific transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that tissue-specific mRNA and long intergenic non-coding RNA (lincRNA) induction differs between individuals with divergent evoked inflammatory responses.
基金supported by the National Natural Science Foundation(82071036,82000973)the Natural Science Foundation of Hunan Province(2022JJ30821,2019JJ50967)the Special Project for the Construction of Innovative Provinces in Hunan Province(2023SK4030),China。
文摘Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.
文摘目的·研究胃癌组织细胞中长链非编码RNA(long-chain non-coding RNA,lncRNA)lincRNA-BBOX1-2的表达对于胃癌诊断及预后判断的价值。方法·实时定量PCR检测45例胃癌组织及癌旁正常组织中lincRNA-BBOX1-2的表达水平,分析lincRNABBOX1-2的表达水平与胃癌患者临床病理特征及预后的关系。结果·胃癌组织中lincRNA-BBOX1-2的表达水平高于癌旁正常组织(3.291±0.274 vs 1.125±0.075,P=0.000);胃癌组织中lincRNA-BBOX1-2的表达水平与肿瘤有/无淋巴结转移(P=0.005,r=0.172)及TNM分期(P=0.013,r=0.137)呈正相关。受试者工作特征曲线分析结果显示:lincRNA-BBOX1-2在预测胃癌发生时,其曲线下面积(area under the curve,AUC)值为0.916(95%CI 0.859~0.972);lincRNA-BBOX1-2在预测胃癌有/无淋巴结转移时,其AUC值为0.720(95%CI 0.565~0.875)。结论·胃癌组织中lincRNA-BBOX1-2的表达水平上调与胃癌的临床病理特征密切相关。lincRNA-BBOX1-2可能成为一个新的胃癌诊断分子标志物。
