Long non-coding RNAs （IncRNAs）, gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence i...Long non-coding RNAs （IncRNAs）, gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indicates that IncRNAs also play a critical role in regulation of carcinogenesis and cancer progression. Here, we will summarize the recent researches about some IncRNAs in the development of cancers, hoping to give a new view about the study in the mechanisms involved in carcinogenesis and tumor progression.展开更多
Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
Objective This study is aimed at observing the role of long noncoding RNAs（lncR NAs） in the pathogenesis of abdominal aortic aneurysm（AAA）.Methods Lnc RNA and m RNA expression signatures of AAA tissues and normal ...Objective This study is aimed at observing the role of long noncoding RNAs（lncR NAs） in the pathogenesis of abdominal aortic aneurysm（AAA）.Methods Lnc RNA and m RNA expression signatures of AAA tissues and normal abdominal aortic tissues（NT） were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR（q RT-PCR）.The lnc RNAs-m RNAs targeting relationships were identified using computational analysis.The effect of lnc-ARG on 5-lipoxygenase（ALOX5） expression was tested in HeL a cells.Results Differential expressions of 3,688 lncR NAs and 3,007 m RNAs were identified between AAA and NT tissues.Moreover,1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lnc RNAs adjacent to protein-coding genes were discerned by bioinformatics analysis.Some differentially expressed lncR NAs and m RNAs between AAA and normal tissue samples were further verified using q RT-PCR.A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lnc RNAs and mR NAs.In addition,the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis.Furthermore,we found that lnc-ARG can decrease the m RNA level of ALOX5 and reactive oxygen species production in He La cells.Conclusion This study revealed new lnc RNA candidates are related to the pathogenesis of AAA.展开更多
Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory functions.They interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular fun...Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory functions.They interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and progression.Recently,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding genes.However,their biological significance in the tumor phenotype is still uncertain.Therefore,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic targets.The present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential function.We address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.展开更多
The activation of NLRC4 is a major host response against intracellular bacteria infection.However,NLRC4 activation after a host senses diverse stimuli is difficult to understand.Here,we found that the IncRNA LNCGM1082...The activation of NLRC4 is a major host response against intracellular bacteria infection.However,NLRC4 activation after a host senses diverse stimuli is difficult to understand.Here,we found that the IncRNA LNCGM1082 plays a critical role in the activation of NLRC4.LNCGM1082 in macrophages affects the maturation of interleukin(IL)-1βand pyroptotic cell death only after exposure to an NLRC4 ligand.Similar to NLRC4-/-mice,LNCGM1082-/-mice were highly sensitive to Salmonella Typhimurium(S.T)infection.LNCGM1082 deficiency in mouse or human macrophages inhibited IL-1βmaturation and pyroptosis.Mechanistically,LNCGM1082 induced the binding of PKCS with NLRC4 in both mice and humans.In contrast,NLRC4 did not bind PKCo in LNCGM1082-/-macrophages.The activity of the IncRNA LNCGM1082 induced by S.T may be mediated through TLR5 in the macrophages of both mice and humans.In summary,our data indicate that TLR5-mediated LNCGM1082 activity can promote the binding of PKC with NLRC4 to activate NLRC4 and induce resistance to bacterial infection.展开更多
文摘Long non-coding RNAs （IncRNAs）, gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indicates that IncRNAs also play a critical role in regulation of carcinogenesis and cancer progression. Here, we will summarize the recent researches about some IncRNAs in the development of cancers, hoping to give a new view about the study in the mechanisms involved in carcinogenesis and tumor progression.
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
基金supported by the grants from National Natural Science Foundation of China(No.81100226,31300889,91439127,and 81570435)
文摘Objective This study is aimed at observing the role of long noncoding RNAs（lncR NAs） in the pathogenesis of abdominal aortic aneurysm（AAA）.Methods Lnc RNA and m RNA expression signatures of AAA tissues and normal abdominal aortic tissues（NT） were analyzed by microarray and further verified by Real-time quantitative reverse-transcription PCR（q RT-PCR）.The lnc RNAs-m RNAs targeting relationships were identified using computational analysis.The effect of lnc-ARG on 5-lipoxygenase（ALOX5） expression was tested in HeL a cells.Results Differential expressions of 3,688 lncR NAs and 3,007 m RNAs were identified between AAA and NT tissues.Moreover,1,284 differentially expressed long intergenic noncoding RNAs and 206 differentially expressed enhancer-like lnc RNAs adjacent to protein-coding genes were discerned by bioinformatics analysis.Some differentially expressed lncR NAs and m RNAs between AAA and normal tissue samples were further verified using q RT-PCR.A co-expression network of coding and noncoding genes was constructed based on the correlation analysis between the differentially expressed lnc RNAs and mR NAs.In addition,the lnc-ARG located within the upstream of ALOX5 was sorted as a noncoding transcript by analyzing the protein-coding potential using computational analysis.Furthermore,we found that lnc-ARG can decrease the m RNA level of ALOX5 and reactive oxygen species production in He La cells.Conclusion This study revealed new lnc RNA candidates are related to the pathogenesis of AAA.
文摘Long non-coding RNAs(lncRNAs)are non-coding RNAs longer than 200 nucleotides with dynamic regulatory functions.They interact with a wide range of molecules such as DNA,RNA,and proteins to modulate diverse cellular functions through several mechanisms and,if deregulated,they can lead to cancer development and progression.Recently,it has been described that IncRNAs are susceptible to form gene fusions with mRNAs or other IncRNAs,breaking the paradigm of gene fusions consisting mainly of protein-coding genes.However,their biological significance in the tumor phenotype is still uncertain.Therefore,their recent identification opens a new line of research to study their biological role in tumor-igenesis,and their potential as biomarkers with clinical relevance or as therapeutic targets.The present study aimed to review the IncRNA fusions identified so far and to know which of them have been associated with a potential function.We address the current challenges to deepen their study as well as the reasons why they represent a future therapeutic window incancer.
基金NSFC grants(grant numbers 81901677,82271779,91842302,81970457,and 91629102)The Tianjin Science and Technology Commission(grant number,18JCZDJC35300)+1 种基金A Ministry of Science and Technology(grant number,2016YFC1303604)The State Key Laboratory of Medicinal Chemical Biology and the Fundamental Research Funds for the Central University,Nankai university(63191724).
文摘The activation of NLRC4 is a major host response against intracellular bacteria infection.However,NLRC4 activation after a host senses diverse stimuli is difficult to understand.Here,we found that the IncRNA LNCGM1082 plays a critical role in the activation of NLRC4.LNCGM1082 in macrophages affects the maturation of interleukin(IL)-1βand pyroptotic cell death only after exposure to an NLRC4 ligand.Similar to NLRC4-/-mice,LNCGM1082-/-mice were highly sensitive to Salmonella Typhimurium(S.T)infection.LNCGM1082 deficiency in mouse or human macrophages inhibited IL-1βmaturation and pyroptosis.Mechanistically,LNCGM1082 induced the binding of PKCS with NLRC4 in both mice and humans.In contrast,NLRC4 did not bind PKCo in LNCGM1082-/-macrophages.The activity of the IncRNA LNCGM1082 induced by S.T may be mediated through TLR5 in the macrophages of both mice and humans.In summary,our data indicate that TLR5-mediated LNCGM1082 activity can promote the binding of PKC with NLRC4 to activate NLRC4 and induce resistance to bacterial infection.
