目的系统评价乳铁蛋白（LTF）基因rs1126478多态性与龋病易感性的关系。方法计算机检索Pubmed,Web of science,Embase,EBSCO,Springerlink,中国知网（CNKI）,维普（VIP）,万方及中国生物医学文献数据库（CBM）,收集发表的有关LTF基因rs1...目的系统评价乳铁蛋白（LTF）基因rs1126478多态性与龋病易感性的关系。方法计算机检索Pubmed,Web of science,Embase,EBSCO,Springerlink,中国知网（CNKI）,维普（VIP）,万方及中国生物医学文献数据库（CBM）,收集发表的有关LTF基因rs1126478多态性与龋病发病风险的文献,以OR及其95%CI为效应指标,运用RevMan 5.2及Stata 12.0软件进行统计学分析,并进行偏倚评估及敏感性分析。结果共纳入5个病例对照研究,累积病例720例,对照412例,Meta分析结果显示,4种模型中LTF基因rs1126478多态性与龋病发病风险相关性无统计学意义（GG＋AGvs.AA：P=0.75,OR=0.93,95%CI=0.59~1.46;Gvs.A：P=0.88,OR=0.97,95%CI=0.68~1.38;GGvs.AA：P=0.84,OR=1.07,95%CI=0.57~1.99;GG vs.AG＋AA：P=0.52,OR=1.12,95%CI=0.79~1.58）,按人种进行亚组分析结果显示,在Caucasian及Asian人群中LTF基因rs1126478多态性与龋病发病风险相关性亦无统计学意义（P〉0.05）。结论乳铁蛋白基因rs1126478多态性可能与龋病易感性无关。展开更多
Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.I...Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.In this study,we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues.By incorporating chromatin immunoprecipitation sequencing data,we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.Among these,lactotransferrin-eRNA(LTFe)was markedly downregulated in prostate cancer tissues,with functional analyses revealing its tumor-suppressive role.Mechanistically,LTFe promotes the transcription of its target gene,lactotransferrin(LTF),by interacting with heterogeneous nuclear ribonucleoprotein F(HNRNPF)and facilitating enhancer-promoter chromatin interactions.Furthermore,we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport.Notably,androgen receptor(AR)signaling disrupts LTFe-associated chromatin looping,leading to ferroptosis resistance.Therapeutically,co-administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth,offering a promising strategy for castrationresistant prostate cancer.Collectively,this study provides novel insights into the mechanistic role of eRNAs in prostate cancer,highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82373333,82173068)to Z.Wang,and Nos.82073082,82311530050 to G.-H.Wei+2 种基金the Hubei Natural Science Foundation Innovation Development Joint Fund Key Project(2024AFD420 to Z.Wang)the National Key Research and Development Program of China(2022YFC2703600 to G.-H.Wei)Z.X.Wang was supported by the National Natural Science Foundation of China(82203416)。
文摘Enhancer RNAs(eRNAs),a subclass of non-coding RNAs transcribed from enhancer regions,have emerged as critical regulators of gene expression;however,their functional roles in prostate cancer remain largely unexplored.In this study,we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues.By incorporating chromatin immunoprecipitation sequencing data,we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways.Among these,lactotransferrin-eRNA(LTFe)was markedly downregulated in prostate cancer tissues,with functional analyses revealing its tumor-suppressive role.Mechanistically,LTFe promotes the transcription of its target gene,lactotransferrin(LTF),by interacting with heterogeneous nuclear ribonucleoprotein F(HNRNPF)and facilitating enhancer-promoter chromatin interactions.Furthermore,we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport.Notably,androgen receptor(AR)signaling disrupts LTFe-associated chromatin looping,leading to ferroptosis resistance.Therapeutically,co-administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth,offering a promising strategy for castrationresistant prostate cancer.Collectively,this study provides novel insights into the mechanistic role of eRNAs in prostate cancer,highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.
