BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance...BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.展开更多
Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury ti...Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.展开更多
目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差...目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。展开更多
目的探究长链非编码RNA UC001kfo在宫颈癌病人中的表达情况及其临床指导意义。方法收集整理2012年4月2日至2017年2月2日云南省第二人民医院不同国际妇产科协会(International Federation of Gynecology and Obstetrics,FIGO)分期手术切...目的探究长链非编码RNA UC001kfo在宫颈癌病人中的表达情况及其临床指导意义。方法收集整理2012年4月2日至2017年2月2日云南省第二人民医院不同国际妇产科协会(International Federation of Gynecology and Obstetrics,FIGO)分期手术切除的宫颈癌及其癌旁组织标本共81例,采用实时荧光定量多聚核苷酸链式反应(qPCR)技术检测UC001kfo表达水平,分析UC001kfo的表达水平与临床病理特征和预后的关系。结果全组病人宫颈癌组织中UC001kfo的表达水平(4.694±1.378)明显高于癌旁组织(1.543±0.598)(P<0.01)。UC001kfo表达水平与宫颈癌病人的FIGO分期、淋巴结转移和肿瘤侵袭关系密切(P<0.05)。Kaplan?Meier分析显示UC001kfo高表达病人的总生存时间明显低于低表达病人(P<0.05)。Cox回归多因素分析显示UC001kfo表达水平、FIGO分期、淋巴结转移和肿瘤侵袭为影响宫颈癌病人总生存时间的独立因素(P<0.05)。结论UC001kfo在宫颈癌组织中高表达,UC001kfo高表达与宫颈癌病人的预后不良有关,UC001kfo或可成为宫颈癌病人潜在的预后标志物。展开更多
基金Supported by the National Natural Science Foundation of China,No.81974372
文摘BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.
基金supported by the National Natural Science Foundation of China,No.81571939(to KX),81601719(to JZ)and 81772134(to KX)Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)Teacher Research Foundation of Central South University of China,No.2014JSJJ026(to KX)
文摘Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.
文摘目的筛选直肠癌新辅助放化疗(CRT)疗效预测长链非编码RNA(lncRNA)分子标志物,分析参与CRT疗效调控相关信号通路,建立CRT疗效预测模型。方法利用lncRNA芯片进行lncRNA差异表达检测,使用R软件Limma包在CRT反应组和CRT无反应组间对比筛选差异lncRNA(P<0.05和|Log2FC|>1),进行分子标志物筛选。采用基因本体(GO)分析对差异表达基因进行功能分析,采用京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)对筛选的差异基因进行信号通路富集分析。进一步采用实时定量反转录聚合酶链式反应(qRT-PCR)检测98例样本。采用logistic回归构建CRT治疗预测模型。绘制受试者操作特征曲线(ROC)计算曲线下面积(AUC)以评价模型的判别区分能力。结果CRT反应组中,823个lncRNA表达上调,216个lncRNA表达下调,449个基因表达上调,81个基因表达下调。新辅助放化疗相关上调排名前10的差异表达lncRNA分别为LUCAT1、LINC02356、HIF1A-AS2、Lnc-ZNF644-1、Lnc-ADAMTS12-3、LINC02356、Lnc-CLIC4-1、Lnc-PTX3-4、DARS-AS1、MIR210HG。下调排名前10的分别为Lnc-COL6A3-2、Lnc-FBN1-2、Lnc-FOXA1-3、Lnc-KRTAP9-7-1、LINC00562、Lnc-NCS1-1、LINC00456、Lnc-FBLL1-2、USP2-AS1、Lnc-INPPL1-2。GO分析结果提示,差异基因主要富集在上皮细胞分化、中间丝、中间丝细胞骨架、突触后膜、颗粒分泌、细胞因子受体活性等分子生物学功能方面。KEGG富集分析提示,差异表达基因主要富集在HIF-1信号通路、Th17细胞分化、戊糖磷酸途径、精氨酸和脯氨酸代谢、果糖和甘露糖代谢、磷脂酶D信号通路、溶酶体等信号通路方面。logistic回归模型显示,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型具有较好的预测能力,AUC为0.887(95%CI 0.820~0.954)。模型回归方程logit(p)=1.582×LINC00562-1.969×LINC02356-0.798×LUCAT1+4.357。模型的灵敏度为81.3%,特异度为84.0%。结论直肠癌CRT反应良好和CRT无反应者间lncRNA分子存在明显的差异表达,由LUCAT1、LINC02356、LINC00562三个lncRNA分子构成的预测模型对CRT疗效具有较好的预测能力。
文摘目的探究长链非编码RNA UC001kfo在宫颈癌病人中的表达情况及其临床指导意义。方法收集整理2012年4月2日至2017年2月2日云南省第二人民医院不同国际妇产科协会(International Federation of Gynecology and Obstetrics,FIGO)分期手术切除的宫颈癌及其癌旁组织标本共81例,采用实时荧光定量多聚核苷酸链式反应(qPCR)技术检测UC001kfo表达水平,分析UC001kfo的表达水平与临床病理特征和预后的关系。结果全组病人宫颈癌组织中UC001kfo的表达水平(4.694±1.378)明显高于癌旁组织(1.543±0.598)(P<0.01)。UC001kfo表达水平与宫颈癌病人的FIGO分期、淋巴结转移和肿瘤侵袭关系密切(P<0.05)。Kaplan?Meier分析显示UC001kfo高表达病人的总生存时间明显低于低表达病人(P<0.05)。Cox回归多因素分析显示UC001kfo表达水平、FIGO分期、淋巴结转移和肿瘤侵袭为影响宫颈癌病人总生存时间的独立因素(P<0.05)。结论UC001kfo在宫颈癌组织中高表达,UC001kfo高表达与宫颈癌病人的预后不良有关,UC001kfo或可成为宫颈癌病人潜在的预后标志物。
