The Experts below are selected from a list of 264093 Experts worldwide ranked by ideXlab platform
Michelle Makiya - One of the best experts on this subject based on the ideXlab platform.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:The long Non-Coding RNA Morrbid controls myeloid cell lifespan and regulates apoptosis by repressing the adjacent pro-apoptotic Bcl2l11 gene in cis. Neutrophils, eosinophils and 'classical' monocytes are a first line of defense against pathogens, but their actions can also cause inflammatory diseases. It is important that the lifespan of these myeloid cells is regulated in order to minimize deleterious effects. Jorge Henao-Mejia and colleagues show here that a long Non-Coding RNA termed Morrbid specifically controls the lifespan of short-lived myeloid cells by regulating expression of the pro-apoptotic Bcl2l11 (Bim) gene. MORRBID is present in humans and is highly upregulated in human hypereosinophilic diseases, so its inhibition may represent a novel therapeutic approach in pathologies influenced by altered myeloid lifespan. Neutrophils, eosinophils and ‘classical’ monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body1,2. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation1,2. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
Sean P Spencer - One of the best experts on this subject based on the ideXlab platform.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:The long Non-Coding RNA Morrbid controls myeloid cell lifespan and regulates apoptosis by repressing the adjacent pro-apoptotic Bcl2l11 gene in cis. Neutrophils, eosinophils and 'classical' monocytes are a first line of defense against pathogens, but their actions can also cause inflammatory diseases. It is important that the lifespan of these myeloid cells is regulated in order to minimize deleterious effects. Jorge Henao-Mejia and colleagues show here that a long Non-Coding RNA termed Morrbid specifically controls the lifespan of short-lived myeloid cells by regulating expression of the pro-apoptotic Bcl2l11 (Bim) gene. MORRBID is present in humans and is highly upregulated in human hypereosinophilic diseases, so its inhibition may represent a novel therapeutic approach in pathologies influenced by altered myeloid lifespan. Neutrophils, eosinophils and ‘classical’ monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body1,2. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation1,2. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
Lianmei Zhao - One of the best experts on this subject based on the ideXlab platform.
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long non coding RNA snhg5 suppresses gastric cancer progression by trapping mta2 in the cytosol
Oncogene, 2016Co-Authors: Lianmei Zhao, B Zhou, J Feng, Yexiong Li, Li Li, Shang Zhang, Dexian ZhengAbstract:Long Non-Coding RNA SNHG5 suppresses gastric cancer progression by trapping MTA2 in the cytosol
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long non coding RNA snhg5 suppresses gastric cancer progression by trapping mta2 in the cytosol
Oncogene, 2016Co-Authors: Lianmei Zhao, B Zhou, J Feng, Huiqin Guo, Tao Han, L Liu, Shuyang Zhang, Yongshuo Liu, Juan ShiAbstract:Recently, intriguing new roles for some small nucleolar RNA host genes (SNHGs) in cancer have emerged. In the present study, a panel of SNHGs was profiled to detect aberrantly expressed SNHGs in gastric cancer (GC). The expression of SNHG5 was significantly downregulated in GC and was significantly associated with the formation of a tumor embolus and with the tumor, node and metastasis stage. SNHG5 was a long Non-Coding RNA, which was a class of Non-Coding RNA transcripts longer than 200 nucleotides. SNHG5 suppressed GC cell proliferation and metastasis in vitro and in vivo. Furthermore, SNHG5 exerted its function through interacting with MTA2, preventing the translocation of MTA2 from the cytoplasm into the nucleus. SNHG5 overexpression led to significant increases in the acetylation levels of histone H3 and p53, indicating that SNHG5 might affect acetylation by trapping MTA2 in the cytosol, thereby interfering with the formation of the nucleosome remodeling and histone deacetylation complex. This study is the first to demonstrate that SNHG5 is a critical and powerful regulator that is involved in GC progression through trapping MTA2 in the cytosol. These results imply that SNHG5 may be a novel therapeutic target for the treatment of GC.
Jonathan J Kotzin - One of the best experts on this subject based on the ideXlab platform.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:The long Non-Coding RNA Morrbid controls myeloid cell lifespan and regulates apoptosis by repressing the adjacent pro-apoptotic Bcl2l11 gene in cis. Neutrophils, eosinophils and 'classical' monocytes are a first line of defense against pathogens, but their actions can also cause inflammatory diseases. It is important that the lifespan of these myeloid cells is regulated in order to minimize deleterious effects. Jorge Henao-Mejia and colleagues show here that a long Non-Coding RNA termed Morrbid specifically controls the lifespan of short-lived myeloid cells by regulating expression of the pro-apoptotic Bcl2l11 (Bim) gene. MORRBID is present in humans and is highly upregulated in human hypereosinophilic diseases, so its inhibition may represent a novel therapeutic approach in pathologies influenced by altered myeloid lifespan. Neutrophils, eosinophils and ‘classical’ monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body1,2. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation1,2. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
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the long non coding RNA morrbid regulates bim and short lived myeloid cell lifespan
Nature, 2016Co-Authors: Jonathan J Kotzin, Sean P Spencer, Sam J Mccright, Dinesh Babu Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle MakiyaAbstract:Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long Non-Coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice. To control the lifespan of these cells, Morrbid regulates the transcription of the neighbouring pro-apoptotic gene, Bcl2l11 (also known as Bim), by promoting the enrichment of the PRC2 complex at the Bcl2l11 promoter to maintain this gene in a poised state. Notably, Morrbid regulates this process in cis, enabling allele-specific control of Bcl2l11 transcription. Thus, in these highly inflammatory cells, changes in Morrbid levels provide a locus-specific regulatory mechanism that allows rapid control of apoptosis in response to extracellular pro-survival signals. As MORRBID is present in humans and dysregulated in individuals with hypereosinophilic syndrome, this long Non-Coding RNA may represent a potential therapeutic target for inflammatory disorders characterized by aberrant short-lived myeloid cell lifespan.
Victoria Eugenia Villegas - One of the best experts on this subject based on the ideXlab platform.
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identification of novel non coding RNA based negative feedback regulating the expression of the oncogenic transcription factor gli1
Molecular Oncology, 2014Co-Authors: Mohammed Ferdous-ur Rahman, Yumei Diao, Eleni A Liapi, Enikö Sonkoly, Mona Stahle, Andor Pivarcsi, Victoria Eugenia Villegas, Maite G Fernandezbarrena, Laura AnnaratoneAbstract:Non-Coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a Non-Coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFβ and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the Non-Coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel Non-Coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor.
