Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular m...Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.展开更多
Induction and mobilization of transposable elements （TEs） following DNA damage or other stresses has been reported in prokaryotes and eukaryotes. Recently it was discovered that eukaryotic TEs are frequently associa...Induction and mobilization of transposable elements （TEs） following DNA damage or other stresses has been reported in prokaryotes and eukaryotes. Recently it was discovered that eukaryotic TEs are frequently associated with long non-coding RNAs （IncRNAs）, many of which are also upregulated by stress. Yet, it is unknown whether DNA damage-induced transcriptional activation of TEs and IncRNAs occurs sporadically or is a synchronized, genome-wide response. Here we investigated the transcriptome of Arabidopsis wild- type （WT） and ataxia telangiectasia mutated （atm） mutant plants 3 h after induction of DNA damage. In WT, expression of 5.2% of the protein-coding genes is 〉 2-fold changed, whereas in atm plants, only 2.6% of these genes are regulated, and the response of genes associated with DNA repair, replication, and cell cy- cle is largely lost. In contrast, only less than 0.6% of TEs and IncRNAs respond to DNA damage in WT plants, and the regulation of 〉95% of them is ATM-dependent. The ATM-downstream factors BRCA1, DRM1, JMJ30, AGO2, and the ATM-independent AGO4 participate in the regulation of individual TEs and IncRNAs. Remarkably, protein-coding genes located adjacent to DNA damage-responsive TEs and IncRNAs are frequently coexpressed, which is consistent with the hypothesis that TEs and IncRNAs located close to genes commonly function as controlling elements.展开更多
Embryonic stern cells （ESCs） and induced pluripotent stem cells （iPSCs） hold immense promise for regenerative medicine due to their abilities to self-renew and to differentiate into all cell types. This unique pro...Embryonic stern cells （ESCs） and induced pluripotent stem cells （iPSCs） hold immense promise for regenerative medicine due to their abilities to self-renew and to differentiate into all cell types. This unique property is controlled by a complex interplay between transcriptional factors and epigenefic regulators. Recent research indicates that the epigenetic role of non-coding RNAs （ncRNAs） is an integral component of this regulatory network. This report will summarize findings that focus on two classes of regulatory ncRNAs, microRNAs （miRNAs） and long ncRNAs （lncRNAs）, in the induction, maintenance and directed differentiation of ESCs and iPSCs. Manipulating these two important types of ncRNAs would be crucial to unlock the therapeutic and research potential of pluripotent stem cells.展开更多
目的:探讨长链非编码RNA(long noncoding RNA,lncRNA)中的反义缺氧诱导因子(antisense hypoxia inducible factor,a HIF)和位于细胞周期激酶抑制因子4(INK4)基因座中反义非编码RNA(antisense noncoding RNA in the INK4 locus,ANRIL)在...目的:探讨长链非编码RNA(long noncoding RNA,lncRNA)中的反义缺氧诱导因子(antisense hypoxia inducible factor,a HIF)和位于细胞周期激酶抑制因子4(INK4)基因座中反义非编码RNA(antisense noncoding RNA in the INK4 locus,ANRIL)在胃癌组织与血浆中的表达。方法:收集20例胃癌患者癌组织及对应的癌旁组织、33例胃癌患者和20例健康者血浆,采用实时荧光定量PCR测定胃癌组织和血浆中lncRNA a HIF和ANRIL的表达水平,分析lncRNA a HIF、ANRIL在血浆中的表达与胃癌组织表达的相关性。结果:胃癌组织中lncRNA a HIF和ANRIL的表达水平均明显高于癌旁组织(t分别为-4.463,-4.886,P均<0.01);胃癌患者血浆中lncRNA a HIF和ANRIL的表达水平均明显高于健康者(t分别为-4.232,-4.450,P<0.01),且与胃癌组织中的表达水平呈正相关(r分别为0.536,0.524,P<0.05)。结论:lncRNA a HIF和ANRIL在胃癌组织和患者血浆中均高表达,且血浆与组织中的表达水平呈正相关。展开更多
基金financially supported by the National Natural Science Foundation of China,No.81371366(to HFW)Characteristic Innovation Project of Colleges and Universities in Guangdong Province of China,No.2018KTSCX075(to HFW)+3 种基金the Key Project of Social Development of Dongguan of China,No.20185071521640(to HFW)College Students’ Science and Technology Innovation Training Project,China,Nos.201810571058,GDMU2018024,GDMU2018056,GDMU2018061(to HFW)College Students’ Innovative Experimental Project in Guangdong Medical University,China,No.ZZDS001(to HFW)College Students’ Science and Technology Innovation Cultivation Project in Guangdong of China,No.pdjh2019b0217(to HFW)
文摘Long non-coding RNAs(lncRNAs)are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes.To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury(SCI),the expression signatures of lncRNAs were profiled using RNA sequencing(RNA-seq)technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI.Results showed that 116 of 14,802 detected lncRNAs were differentially expressed,among which 16—including eight up-regulated(H19,Vof16,Hmox2-ps1,LOC100910973,Ybx1-ps3,Nnat,Gcgr,LOC680254)and eight down-regulated(Rmrp,Terc,Ngrn,Ppp2r2b,Cox6a2,Rpl37a-ps1,LOC360231,Rpph1)—demonstrated fold changes>2 in response to transection SCI.A subset of these RNA-seq results was validated by quantitative real-time PCR.The levels of 821 mRNAs were also significantly altered post-SCI;592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response,wound repair,and apoptosis,and were significantly enriched in 15 KEGG pathways,including cell phagocytosis,tumor necrosis factor alpha pathway,and leukocyte migration.Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model,and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment.We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury.This study was approved by the Administration Committee of Experimental Animals,Guangdong Province,China.
文摘Induction and mobilization of transposable elements （TEs） following DNA damage or other stresses has been reported in prokaryotes and eukaryotes. Recently it was discovered that eukaryotic TEs are frequently associated with long non-coding RNAs （IncRNAs）, many of which are also upregulated by stress. Yet, it is unknown whether DNA damage-induced transcriptional activation of TEs and IncRNAs occurs sporadically or is a synchronized, genome-wide response. Here we investigated the transcriptome of Arabidopsis wild- type （WT） and ataxia telangiectasia mutated （atm） mutant plants 3 h after induction of DNA damage. In WT, expression of 5.2% of the protein-coding genes is 〉 2-fold changed, whereas in atm plants, only 2.6% of these genes are regulated, and the response of genes associated with DNA repair, replication, and cell cy- cle is largely lost. In contrast, only less than 0.6% of TEs and IncRNAs respond to DNA damage in WT plants, and the regulation of 〉95% of them is ATM-dependent. The ATM-downstream factors BRCA1, DRM1, JMJ30, AGO2, and the ATM-independent AGO4 participate in the regulation of individual TEs and IncRNAs. Remarkably, protein-coding genes located adjacent to DNA damage-responsive TEs and IncRNAs are frequently coexpressed, which is consistent with the hypothesis that TEs and IncRNAs located close to genes commonly function as controlling elements.
基金supported by grants from the Ministry of Science and Technology of China(Grant No.2011CB965100,2011DFA30480,2010CB944900,2010CB945000,2012CB966603,2011CBA01100 and 2013CB967401)the National Natural Science Foundation of China(Grant No.31210103905,91219305,31201107,31101061,81170499,31071306,31000378 and 31171432)+2 种基金the Science and Technology Commission of Shanghai Municipality(Grant No.12ZR1450900,11ZR1438500 and 11XD1405300)Ministry of Education of China(Grant No.IRT1168 and 20110072110039)supported by Fundamental Research Funds for the Central Universities(Grant No.2000219066,2000219067 and 2000219077)
文摘Embryonic stern cells （ESCs） and induced pluripotent stem cells （iPSCs） hold immense promise for regenerative medicine due to their abilities to self-renew and to differentiate into all cell types. This unique property is controlled by a complex interplay between transcriptional factors and epigenefic regulators. Recent research indicates that the epigenetic role of non-coding RNAs （ncRNAs） is an integral component of this regulatory network. This report will summarize findings that focus on two classes of regulatory ncRNAs, microRNAs （miRNAs） and long ncRNAs （lncRNAs）, in the induction, maintenance and directed differentiation of ESCs and iPSCs. Manipulating these two important types of ncRNAs would be crucial to unlock the therapeutic and research potential of pluripotent stem cells.
文摘目的:探讨长链非编码RNA(long noncoding RNA,lncRNA)中的反义缺氧诱导因子(antisense hypoxia inducible factor,a HIF)和位于细胞周期激酶抑制因子4(INK4)基因座中反义非编码RNA(antisense noncoding RNA in the INK4 locus,ANRIL)在胃癌组织与血浆中的表达。方法:收集20例胃癌患者癌组织及对应的癌旁组织、33例胃癌患者和20例健康者血浆,采用实时荧光定量PCR测定胃癌组织和血浆中lncRNA a HIF和ANRIL的表达水平,分析lncRNA a HIF、ANRIL在血浆中的表达与胃癌组织表达的相关性。结果:胃癌组织中lncRNA a HIF和ANRIL的表达水平均明显高于癌旁组织(t分别为-4.463,-4.886,P均<0.01);胃癌患者血浆中lncRNA a HIF和ANRIL的表达水平均明显高于健康者(t分别为-4.232,-4.450,P<0.01),且与胃癌组织中的表达水平呈正相关(r分别为0.536,0.524,P<0.05)。结论:lncRNA a HIF和ANRIL在胃癌组织和患者血浆中均高表达,且血浆与组织中的表达水平呈正相关。
