BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new ...BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.展开更多
目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照...目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。展开更多
Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is s...Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).展开更多
Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thali...Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thaliana.This mechanistically challenging process results from multiple inputs including gene interactions,cellular geometry,growth rates,and coordinated cell divisions.To better understand how this complex genetic and cellular information controls leaf growth,we developed a mathematical model of flat leaf production.This two-dimensional model describes the gene interactions in a vertex network of cells which grow and divide according to physical forces and genetic information.Interestingly,the model predicts the presence of an unknown additional factor required for the formation of biologically realistic gene expression domains and iterative cell division.This two-dimensional model will form the basis for future studies into robustness of adaxial-abaxial patterning.展开更多
The vegetative development of cabbage(Brassica oleracea var.capitata)passes through seedling,rosette,folding and heading stages.Leaves that form the rosette are large and mostly flat.In the following developmental sta...The vegetative development of cabbage(Brassica oleracea var.capitata)passes through seedling,rosette,folding and heading stages.Leaves that form the rosette are large and mostly flat.In the following developmental stages,the plants produce leaves that curve inward to produce the leafy head.Many microRNAs and their target genes have been described participating in leaf development and leaf curvature.The aim of this study is to investigate the role of miRNA-regulated genes in the transition from the rosette to the heading stage.We compared the mi RNA and gene abundances between emerging rosette and heading leaves.To remove transcripts(miRNAs and genes)whose regulation was most likely associated with plant age rather than the change from rosette to heading stage,we utilized a non-heading collard green(B.oleracea var.acephala)morphotype as control.This resulted in 33 DEMs and 1998 DEGs with likely roles in the transition from rosette to heading stage in cabbage.Among these 1998 DEGs,we found enriched GO terms related to DNA-binding transcription factor activity,transcription regulator activity,iron ion binding,and photosynthesis.We predicted the target genes of these 33 DEMs and focused on the subset that was differentially expressed(1998DEGs)between rosette and heading stage leaves to construct mi RNA-target gene interaction networks.Our main finding is a role for miR396b-5p targeting two Arabidopsis thaliana orthologues of GROWTH REGULATING FACTORs 3(GRF3)and 4(GRF4)in pointed cabbage head formation.展开更多
AIM: To explore the m RNA and pathways related to retinoblastoma(RB) genesis and development.METHODS: Microarray datasets GSE29683(human) and GSE29685(mouse) were downloaded from NCBI GEO database. Homologous genes be...AIM: To explore the m RNA and pathways related to retinoblastoma(RB) genesis and development.METHODS: Microarray datasets GSE29683(human) and GSE29685(mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction(PPI) network construction and gene enrichment analysis. Disease-related mi RNAs and pathways were retrieved from mi R2 Disease database and Comparative Toxicogenomics Database(CTD), respectively.RESULTS: A total of 352 homologous genes were identified. Two pathways including "cell cycle" and "pathway in cancer" in CTD and enrichment analysis were identified and seven mi RNAs(including hsa-mi R-373, hsa-mi R-34 a, hsami R-129, hsa-mi R-494, hsa-mi R-503, hsa-let-7 and hsami R-518 c) were associated with RB. mi RNAs modulate "cell cycle" and "pathway in cancer" pathways via regulating 13 genes(including CCND1, CDC25 C, E2 F2, CDKN2 D and TGFB2).CONCLUSION: These results suggest that these mi RNAs play crucial roles in RB genesis through "cell cycle" and "pathway in cancer" pathways by regulating their targets including CCND1, CDC25 C, E2 F2 and CDKN2 D.展开更多
Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of righ...Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.展开更多
目的通过分析癌症基因组图谱(the cancer genome atlas,TCGA)数据库构建三阴性乳腺癌(triple negative breast cancer,TNBC)预后相关的竞争性内源性核糖核酸(competitive endogenous RNA,ceRNA)调控网络。方法从TCGA数据库中下载TNBC ln...目的通过分析癌症基因组图谱(the cancer genome atlas,TCGA)数据库构建三阴性乳腺癌(triple negative breast cancer,TNBC)预后相关的竞争性内源性核糖核酸(competitive endogenous RNA,ceRNA)调控网络。方法从TCGA数据库中下载TNBC lncRNA表达RNAseq数据,对TNBC患者的mRNA,miRNA和lncRNA进行差异表达分析,并进一步行生存分析,得到与乳腺癌有明显差异表达同时也对生存有相关性的mRNA,miRNA和lncRNA。同时构建lncRNA-miRNA-mRNA相关ceRNA调控网,再对生存相关lncRNA所相关的mRNA进一步功能富集和注释,并构建蛋白质互作网络最终用关键基因通过人类蛋白质图谱(the human protein atlas,HPA)数据库进行验证。结果在TCGA中共找到TNBC差异表达mRNA 2331个、差异miRNA 100个和差异lncRNA 1269个。ceRNA调控网中的mRNA在细胞黏附、唾液分泌和血小板活化、用于IgA产生的肠道免疫网络、补体和凝血级联反应等信号通路中明显富集。生存分析中,1个差异mRNA(NMUR1),1个差异表达miRNA(hsa-miR-6832-3p),2个差异表达的lncRNA(AC104809,LINC01297)的表达量均与TNBC患者的预后相关,差异具有统计学意义(P<0.05)。最后利用HPA数据库对NMUR1蛋白水平和生存分析验证,NMUR1的高表达患者的总生存期显著高于NMUR1低表达组,差异有统计学意义(P<0.05)。结论成功构建了促进TNBC发生发展的lncRNA-miRNA-mRNA调控网络,筛选得到生存相关的差异mRNA,miRNA和lncRNA为TNBC发病机制的研究和诊疗生物标志物的探索提供参考依据。展开更多
RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure...RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure.Thus,how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions.Anisotropic network model(ANM)is an efficient method to investigate macromolecular dynamical properties,which has been widely used in protein studies.However,the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins.In this study,we proposed a new approach,named force-constant-decayed anisotropic network model(fcdANM),to improve the performance in investigating the dynamical properties encoded in RNA structures.In fcd-ANM,nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength.The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs.The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures,and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05%compared to the conventional ANM.Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties.展开更多
基金Supported by the National Natural Science Foundation of China,No.81774093,No.81904009,No.81974546 and No.82174182Key R&D Project of Hubei Province,No.2020BCB001.
文摘BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.
文摘目的研究中药复方桃红四物汤(Tao Hong Si Wu decoction,THSWD)治疗大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠长链非编码RNA(long non-coding RNA,lncRNA)的表达,并确定THSWD治疗MCAO大鼠可能的分子机制。方法从对照组、MCAO组和MCAO+THSWD组各获得3个大脑半球组织。采用RNA测序技术鉴定三组中的lncRNA基因表达。鉴定了THSWD调节的lncRNA基因,然后构建了THSWD调节的lncRNA-mRNA网络。通过MCODE插件鉴定lncRNA-mRNA网络的模块。基因本体(gene ontology,GO)和京都基因与基因组百科全书数据库(kyoto encyclopedia of genes and genomes,KEGG)用于分析富集的生物功能和信号通路。鉴定了THSWD调节的lncRNA的顺式和反式调控基因。采用逆转录实时定量聚合酶链式反应(RT-qPCR)验证lncRNA。分子对接用于验证lncRNA-mRNA网络靶点和通路相关蛋白结合能力。结果在MCAO大鼠中,THSWD共调节了302个lncRNA。生物信息学分析表明,一些核心lncRNA可能在THSWD治疗MCAO大鼠中发挥重要作用,此外,我们进一步发现THSWD可能也通过lncRNA-mRNA网络以及网络富集的补体和凝血级联反应等多通路治疗MCAO大鼠。分子对接结果表明,THSWD活性化合物没食子酸和苦杏仁苷与蛋白质靶点具有一定的结合能力。结论THSWD可以通过调节lncRNA保护MCAO大鼠脑损伤,为THSWD治疗缺血性中风提供了新见解。
基金supported by the Notional Natural Science Foundation of China,No.81960417 (to JX)Guangxi Key Research and Development Program,No.GuiKeA B20159027 (to JX)the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2022GXNSFBA035545 (to YG)。
文摘Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).
基金supported by the NSF#2039489 to A.Y.H and the NSF#1813071 to C.-S.C.
文摘Biology provides many examples of complex systems whose properties allow organisms to develop in a highly reproducible,or robust,manner.One such system is the growth and development of flat leaves in Arabidopsis thaliana.This mechanistically challenging process results from multiple inputs including gene interactions,cellular geometry,growth rates,and coordinated cell divisions.To better understand how this complex genetic and cellular information controls leaf growth,we developed a mathematical model of flat leaf production.This two-dimensional model describes the gene interactions in a vertex network of cells which grow and divide according to physical forces and genetic information.Interestingly,the model predicts the presence of an unknown additional factor required for the formation of biologically realistic gene expression domains and iterative cell division.This two-dimensional model will form the basis for future studies into robustness of adaxial-abaxial patterning.
基金funded by the Mexican government through the Consejo Nacional de Ciencia y Tecnología (CONACYT),C.V.761325,for the PhD project of Jorge Aleman-Baez。
文摘The vegetative development of cabbage(Brassica oleracea var.capitata)passes through seedling,rosette,folding and heading stages.Leaves that form the rosette are large and mostly flat.In the following developmental stages,the plants produce leaves that curve inward to produce the leafy head.Many microRNAs and their target genes have been described participating in leaf development and leaf curvature.The aim of this study is to investigate the role of miRNA-regulated genes in the transition from the rosette to the heading stage.We compared the mi RNA and gene abundances between emerging rosette and heading leaves.To remove transcripts(miRNAs and genes)whose regulation was most likely associated with plant age rather than the change from rosette to heading stage,we utilized a non-heading collard green(B.oleracea var.acephala)morphotype as control.This resulted in 33 DEMs and 1998 DEGs with likely roles in the transition from rosette to heading stage in cabbage.Among these 1998 DEGs,we found enriched GO terms related to DNA-binding transcription factor activity,transcription regulator activity,iron ion binding,and photosynthesis.We predicted the target genes of these 33 DEMs and focused on the subset that was differentially expressed(1998DEGs)between rosette and heading stage leaves to construct mi RNA-target gene interaction networks.Our main finding is a role for miR396b-5p targeting two Arabidopsis thaliana orthologues of GROWTH REGULATING FACTORs 3(GRF3)and 4(GRF4)in pointed cabbage head formation.
基金Supported by the Youth Program of National natural science foundation(2018)of China(No.81802998)2019 Basic Research Natural Science Foundation(No.20190201150JC)the Norman Bethune Program of Jilin University(No.2015327)。
文摘AIM: To explore the m RNA and pathways related to retinoblastoma(RB) genesis and development.METHODS: Microarray datasets GSE29683(human) and GSE29685(mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction(PPI) network construction and gene enrichment analysis. Disease-related mi RNAs and pathways were retrieved from mi R2 Disease database and Comparative Toxicogenomics Database(CTD), respectively.RESULTS: A total of 352 homologous genes were identified. Two pathways including "cell cycle" and "pathway in cancer" in CTD and enrichment analysis were identified and seven mi RNAs(including hsa-mi R-373, hsa-mi R-34 a, hsami R-129, hsa-mi R-494, hsa-mi R-503, hsa-let-7 and hsami R-518 c) were associated with RB. mi RNAs modulate "cell cycle" and "pathway in cancer" pathways via regulating 13 genes(including CCND1, CDC25 C, E2 F2, CDKN2 D and TGFB2).CONCLUSION: These results suggest that these mi RNAs play crucial roles in RB genesis through "cell cycle" and "pathway in cancer" pathways by regulating their targets including CCND1, CDC25 C, E2 F2 and CDKN2 D.
文摘Long noncoding RNAs(lncRNAs)participate in a variety of biological processes and diseases.However,the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed.In this study of right side hemisection of the spinal cord at T10,we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed.We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2,the two expression trends with the most significant difference.Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury.There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25.The co-expression network showed that the co-expressed genes were mainly enriched in cell division,inflammatory response,FcγR-mediated cell phagocytosis signaling pathway,cell cycle and apoptosis.The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury.There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2.The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction.The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways.These findings provide a new direction for the clinical treatment of spinal cord injury.
文摘目的通过分析癌症基因组图谱(the cancer genome atlas,TCGA)数据库构建三阴性乳腺癌(triple negative breast cancer,TNBC)预后相关的竞争性内源性核糖核酸(competitive endogenous RNA,ceRNA)调控网络。方法从TCGA数据库中下载TNBC lncRNA表达RNAseq数据,对TNBC患者的mRNA,miRNA和lncRNA进行差异表达分析,并进一步行生存分析,得到与乳腺癌有明显差异表达同时也对生存有相关性的mRNA,miRNA和lncRNA。同时构建lncRNA-miRNA-mRNA相关ceRNA调控网,再对生存相关lncRNA所相关的mRNA进一步功能富集和注释,并构建蛋白质互作网络最终用关键基因通过人类蛋白质图谱(the human protein atlas,HPA)数据库进行验证。结果在TCGA中共找到TNBC差异表达mRNA 2331个、差异miRNA 100个和差异lncRNA 1269个。ceRNA调控网中的mRNA在细胞黏附、唾液分泌和血小板活化、用于IgA产生的肠道免疫网络、补体和凝血级联反应等信号通路中明显富集。生存分析中,1个差异mRNA(NMUR1),1个差异表达miRNA(hsa-miR-6832-3p),2个差异表达的lncRNA(AC104809,LINC01297)的表达量均与TNBC患者的预后相关,差异具有统计学意义(P<0.05)。最后利用HPA数据库对NMUR1蛋白水平和生存分析验证,NMUR1的高表达患者的总生存期显著高于NMUR1低表达组,差异有统计学意义(P<0.05)。结论成功构建了促进TNBC发生发展的lncRNA-miRNA-mRNA调控网络,筛选得到生存相关的差异mRNA,miRNA和lncRNA为TNBC发病机制的研究和诊疗生物标志物的探索提供参考依据。
基金Supported by National Natural Science Foundation of China under Grant Nos. 10802043 and 10832006, Program for Science ＆ Technology Innovation Talents in Universities of Henan under Grant No. 2009HASTIT033 and Key Disciplines of Shanghai municipality （$30104）
文摘RNA is an important biological macromolecule,which plays an irreplaceable role in many life activities.RNA functions are largely determined by its tertiary structure and the intrinsic dynamics encoded in the structure.Thus,how to effective extract structure-encoded dynamics is of great significance for understanding RNA functions.Anisotropic network model(ANM)is an efficient method to investigate macromolecular dynamical properties,which has been widely used in protein studies.However,the performance of the conventional ANM in describing RNA flexibility is not as good as that on proteins.In this study,we proposed a new approach,named force-constant-decayed anisotropic network model(fcdANM),to improve the performance in investigating the dynamical properties encoded in RNA structures.In fcd-ANM,nucleotide pairs in RNA structure were connected by springs and the force constant of springs was decayed exponentially based on the separation distance to describe the differences in the inter-nucleotide interaction strength.The performance of fcd-ANM in predicting RNA flexibility was evaluated using a non-redundant structure database composed of 51 RNAs.The results indicate that fcd-ANM significantly outperforms the conventional ANM in reproducing the experimental B-factors of nucleotides in RNA structures,and the Pearson correlation coefficient between the predicted and experimental nucleotide B-factors was distinctly improved by 21.05%compared to the conventional ANM.Fcd-ANM can serve as a more effective method for analysis of RNA dynamical properties.
