Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development ...Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development of tumors,cardiovascular diseases,nervous system disorders,nephropathy,and other diseases.The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases.This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of IncRNAs from the role of disease coding to acting as drug candidates,including the current status and progress in preclinical research.Cutting-edge strategies for lncRNA modulation have been summarized,including the sources of LncRNA-related drugs,such as genetic technology and small-molecule compounds,and related delivery methods.The current progress of clinical trials of lncRNA-targeting drugs is also discussed.This information will form a latest updated reference for research and development of lncRNA-based drugs.展开更多
Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with populat...Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with population ageing.Long noncoding(lnc)RNAs are transcripts longer than 200 nucleotides that are not translated into proteins,but play important regulatory roles in transcriptional and post-transcriptional regulation.Their contribution to disease onset and development is increasingly recognized.Herein,we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools.Firstly,current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication,fragility fractures,is reviewed.We analyze evidence of their roles in osteogenesis,osteoclastogenesis,and bone fracture healing events from human and animal model studies.Secondly,the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis.Finally,we conclude debating the possibilities,persisting difficulties,and future prospects of using lncRNAs in the treatment of osteoporosis.展开更多
Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of RNA transcripts that do not code for proteins. These non-coding RN...Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of RNA transcripts that do not code for proteins. These non-coding RNAs(nc RNAs) highlight the central role of RNA in gene regulation. nc RNAs are arbitrarily divided into two main groups: The first includes small RNAs, such as mi RNAs, pi RNAs, and endogenous si RNAs, that usually range from 20 to 30 nt, while the second group includes long non-coding RNAs(lnc RNAs), which are typically more than 200 nt in length. These nc RNAs were initially thought to merely regulate gene expression at the post-transcriptional level, but recent studies have indicated that nc RNAs, especially lnc RNAs, are extensively associated with diverse chromatin remodeling complexes and target them to specific genomic loci to alter DNA methylation or histone status. These findings suggest an emerging theme of nc RNAs in epigenetic regulation. In this review, we discuss the wide spectrum of nc RNAs in the regulation of DNA methylation and chromatin state, as well as the key questions that needs to be investigated and acknowledging the elegant design of these intriguing macromolecules.展开更多
Long non-coding RNAs(lncRNAs)is a type of RNA over 200 nt long without any protein coding ability,which has been investigated relating to crucial biological function in cells.There are many key lncRNAs in tumor/normal...Long non-coding RNAs(lncRNAs)is a type of RNA over 200 nt long without any protein coding ability,which has been investigated relating to crucial biological function in cells.There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment.However,compared to some small non-coding RNA,lncRNA-based drugs are limited in clinical application.Different from other non-coding RNA,like microRNAs,most lncRNAs have a high molecular weight and conserved secondary structure,making the delivery of lncRNAs more complex than the small non-coding RNAs.Considering that lncRNAs constitute the most abundant part of the mammalian genome,it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application.In this review,we will discuss the function and mechanism of lncRNAs in diseases,especially cancer,and different approaches for lncRNA transfection using multiple biomaterials.展开更多
目的构建基于坏死性凋亡相关的长链非编码RNAs(necroptosis-related long non-coding RNAs,NRLs)的肝细胞癌预后模型。方法从TCGA数据库下载肝细胞癌的转录本数据和临床信息。采用LASSO-Cox模型构建预后预测模型,受试者工作特征曲线(rec...目的构建基于坏死性凋亡相关的长链非编码RNAs(necroptosis-related long non-coding RNAs,NRLs)的肝细胞癌预后模型。方法从TCGA数据库下载肝细胞癌的转录本数据和临床信息。采用LASSO-Cox模型构建预后预测模型,受试者工作特征曲线(receiver operating characteristic curve,ROC)和校准曲线评估该模型的预测价值,并进行基因集富集分析(gene set enrichment analysis,GSEA)和免疫浸润分析。qRT-PCR验证4个NRLs在肝细胞癌细胞Huh7和正常肝细胞MIHA中的差异表达。结果本研究构建了基于AL117336.2、MKLN1-AS、FOXD2-AS1、LINC01224等4个NRLs的肝细胞癌风险预后模型。基于训练集构建的风险评分是预后的独立影响因素(HR=1.275,P<0.001)。在训练集中,风险模型预测1、3、5年OS的AUC分别为0.816、0.747、0.752,在测试集中分别为0.713、0.621、0.626,且校准曲线显示模型有较好的一致性。根据中位风险评分将患者划分为高、低风险组,训练集和测试集中高风险组的总存活率均低于低风险组(均P<0.05)。此外,不同风险组中免疫细胞浸润程度和免疫检查点分子的表达差异有统计学意义(均P<0.05)。qRT-PCR检测结果显示,4个NRLs在肝细胞癌细胞Huh7中的表达水平均高于正常肝细胞MIHA(均P<0.05)。结论本研究成功构建了预测肝细胞癌患者预后的NRLs模型,对指导临床治疗具有潜在的价值。展开更多
基金supported by the Drug Innovation Major Project of China(Grant No.2018ZX09711001-002-010)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Grant No.2016-I2M-3e011,China)Beijing Natural Science Foundation(Grant Nos.7202138 and 7181007,China)
文摘Enormous studies have corroborated that long non-codig RNAs(LncRNAs)extensively participate in crucial physiological processes such as metabolism and immunity,and are closely related to the occurrence and development of tumors,cardiovascular diseases,nervous system disorders,nephropathy,and other diseases.The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases.This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of IncRNAs from the role of disease coding to acting as drug candidates,including the current status and progress in preclinical research.Cutting-edge strategies for lncRNA modulation have been summarized,including the sources of LncRNA-related drugs,such as genetic technology and small-molecule compounds,and related delivery methods.The current progress of clinical trials of lncRNA-targeting drugs is also discussed.This information will form a latest updated reference for research and development of lncRNA-based drugs.
基金supported by Portuguese funds through FCT—Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia,Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031402—R2Bonethe PORTUGAL 2020 Partnership Agreement,through ERDF+1 种基金FCT DL 57/2016/CP1360/CT0008 (M.I.A.)SFRH/BD/112832/2015 (J.H.T)
文摘Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk,particularly in the vertebrae and the hip.This condition and associated morbidity and mortality increase with population ageing.Long noncoding(lnc)RNAs are transcripts longer than 200 nucleotides that are not translated into proteins,but play important regulatory roles in transcriptional and post-transcriptional regulation.Their contribution to disease onset and development is increasingly recognized.Herein,we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools.Firstly,current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication,fragility fractures,is reviewed.We analyze evidence of their roles in osteogenesis,osteoclastogenesis,and bone fracture healing events from human and animal model studies.Secondly,the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis.Finally,we conclude debating the possibilities,persisting difficulties,and future prospects of using lncRNAs in the treatment of osteoporosis.
文摘Recent deep sequencing surveys of mammalian genomes have unexpectedly revealed pervasive and complex transcription and identified tens of thousands of RNA transcripts that do not code for proteins. These non-coding RNAs(nc RNAs) highlight the central role of RNA in gene regulation. nc RNAs are arbitrarily divided into two main groups: The first includes small RNAs, such as mi RNAs, pi RNAs, and endogenous si RNAs, that usually range from 20 to 30 nt, while the second group includes long non-coding RNAs(lnc RNAs), which are typically more than 200 nt in length. These nc RNAs were initially thought to merely regulate gene expression at the post-transcriptional level, but recent studies have indicated that nc RNAs, especially lnc RNAs, are extensively associated with diverse chromatin remodeling complexes and target them to specific genomic loci to alter DNA methylation or histone status. These findings suggest an emerging theme of nc RNAs in epigenetic regulation. In this review, we discuss the wide spectrum of nc RNAs in the regulation of DNA methylation and chromatin state, as well as the key questions that needs to be investigated and acknowledging the elegant design of these intriguing macromolecules.
基金supported by Southern Medical University,Chinasupported by Fred Eshelman Distinguished Professorship。
文摘Long non-coding RNAs(lncRNAs)is a type of RNA over 200 nt long without any protein coding ability,which has been investigated relating to crucial biological function in cells.There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment.However,compared to some small non-coding RNA,lncRNA-based drugs are limited in clinical application.Different from other non-coding RNA,like microRNAs,most lncRNAs have a high molecular weight and conserved secondary structure,making the delivery of lncRNAs more complex than the small non-coding RNAs.Considering that lncRNAs constitute the most abundant part of the mammalian genome,it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application.In this review,we will discuss the function and mechanism of lncRNAs in diseases,especially cancer,and different approaches for lncRNA transfection using multiple biomaterials.
文摘目的构建基于坏死性凋亡相关的长链非编码RNAs(necroptosis-related long non-coding RNAs,NRLs)的肝细胞癌预后模型。方法从TCGA数据库下载肝细胞癌的转录本数据和临床信息。采用LASSO-Cox模型构建预后预测模型,受试者工作特征曲线(receiver operating characteristic curve,ROC)和校准曲线评估该模型的预测价值,并进行基因集富集分析(gene set enrichment analysis,GSEA)和免疫浸润分析。qRT-PCR验证4个NRLs在肝细胞癌细胞Huh7和正常肝细胞MIHA中的差异表达。结果本研究构建了基于AL117336.2、MKLN1-AS、FOXD2-AS1、LINC01224等4个NRLs的肝细胞癌风险预后模型。基于训练集构建的风险评分是预后的独立影响因素(HR=1.275,P<0.001)。在训练集中,风险模型预测1、3、5年OS的AUC分别为0.816、0.747、0.752,在测试集中分别为0.713、0.621、0.626,且校准曲线显示模型有较好的一致性。根据中位风险评分将患者划分为高、低风险组,训练集和测试集中高风险组的总存活率均低于低风险组(均P<0.05)。此外,不同风险组中免疫细胞浸润程度和免疫检查点分子的表达差异有统计学意义(均P<0.05)。qRT-PCR检测结果显示,4个NRLs在肝细胞癌细胞Huh7中的表达水平均高于正常肝细胞MIHA(均P<0.05)。结论本研究成功构建了预测肝细胞癌患者预后的NRLs模型,对指导临床治疗具有潜在的价值。
