PubMed:25183011 JSONTXT

{"project":"GlyCosmos6-Glycan-Motif-Image","denotations":[{"id":"T1","span":{"begin":204,"end":223},"obj":"Glycan_Motif"},{"id":"T2","span":{"begin":225,"end":233},"obj":"Glycan_Motif"},{"id":"T4","span":{"begin":310,"end":318},"obj":"Glycan_Motif"}],"attributes":[{"id":"A1","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G64581RP"},{"id":"A2","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G89565QL"},{"id":"A3","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G49108TO"},{"id":"A4","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G89565QL"},{"id":"A5","pred":"image","subj":"T4","obj":"https://api.glycosmos.org/wurcs2image/0.10.0/png/binary/G49108TO"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"Glycosmos6-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":225,"end":233},"obj":"GlycoEpitope"},{"id":"T2","span":{"begin":310,"end":318},"obj":"GlycoEpitope"}],"attributes":[{"id":"A1","pred":"glyco_epitope_db_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0004"},{"id":"A2","pred":"glyco_epitope_db_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0004"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos6-Glycan-Motif-Structure","denotations":[{"id":"T1","span":{"begin":204,"end":223},"obj":"https://glytoucan.org/Structures/Glycans/G64581RP"},{"id":"T2","span":{"begin":225,"end":233},"obj":"https://glytoucan.org/Structures/Glycans/G49108TO"},{"id":"T3","span":{"begin":225,"end":233},"obj":"https://glytoucan.org/Structures/Glycans/G89565QL"},{"id":"T4","span":{"begin":310,"end":318},"obj":"https://glytoucan.org/Structures/Glycans/G49108TO"},{"id":"T5","span":{"begin":310,"end":318},"obj":"https://glytoucan.org/Structures/Glycans/G89565QL"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":85},"obj":"Sentence"},{"id":"T2","span":{"begin":86,"end":175},"obj":"Sentence"},{"id":"T3","span":{"begin":176,"end":423},"obj":"Sentence"},{"id":"T4","span":{"begin":424,"end":679},"obj":"Sentence"},{"id":"T5","span":{"begin":680,"end":783},"obj":"Sentence"},{"id":"T6","span":{"begin":784,"end":856},"obj":"Sentence"},{"id":"T7","span":{"begin":857,"end":1001},"obj":"Sentence"},{"id":"T8","span":{"begin":1002,"end":1237},"obj":"Sentence"},{"id":"T9","span":{"begin":1238,"end":1354},"obj":"Sentence"},{"id":"T10","span":{"begin":1355,"end":1483},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T2","span":{"begin":169,"end":174},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T3","span":{"begin":483,"end":488},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T4","span":{"begin":573,"end":578},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T5","span":{"begin":650,"end":655},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T6","span":{"begin":1309,"end":1314},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"T7","span":{"begin":1440,"end":1445},"obj":"http://purl.obolibrary.org/obo/MAT_0000036"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":453,"end":456},"obj":"gene:10724"},{"id":"T1","span":{"begin":650,"end":663},"obj":"disease:C0018802"},{"id":"T2","span":{"begin":453,"end":456},"obj":"gene:10724"},{"id":"T3","span":{"begin":650,"end":663},"obj":"disease:C0018801"},{"id":"T4","span":{"begin":453,"end":456},"obj":"gene:10724"},{"id":"T5","span":{"begin":573,"end":586},"obj":"disease:C0018802"},{"id":"T6","span":{"begin":453,"end":456},"obj":"gene:10724"},{"id":"T7","span":{"begin":573,"end":586},"obj":"disease:C0018801"},{"id":"T8","span":{"begin":1371,"end":1378},"obj":"gene:664612"},{"id":"T9","span":{"begin":1464,"end":1482},"obj":"disease:C0025517"},{"id":"T10","span":{"begin":1371,"end":1378},"obj":"gene:664612"},{"id":"T11","span":{"begin":1440,"end":1453},"obj":"disease:C0018802"},{"id":"T12","span":{"begin":1371,"end":1378},"obj":"gene:664612"},{"id":"T13","span":{"begin":1440,"end":1453},"obj":"disease:C0018801"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"},{"id":"R7","pred":"associated_with","subj":"T12","obj":"T13"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":573,"end":586},"obj":"HP_0001635"},{"id":"T2","span":{"begin":650,"end":663},"obj":"HP_0001635"},{"id":"T3","span":{"begin":1440,"end":1453},"obj":"HP_0001635"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"NGLY1-deficiency","denotations":[{"id":"PD-NGLY1-deficiency-B_T1","span":{"begin":204,"end":223},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T2","span":{"begin":227,"end":233},"obj":"chem:24139"},{"id":"PD-NGLY1-deficiency-B_T3","span":{"begin":312,"end":318},"obj":"chem:24139"}],"namespaces":[{"prefix":"hgnc","uri":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:"},{"prefix":"omim","uri":"https://www.omim.org/entry/"},{"prefix":"chem","uri":"https://pubchem.ncbi.nlm.nih.gov/compound/"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"25183011-3#29#32#gene10724","span":{"begin":453,"end":456},"obj":"gene10724"},{"id":"25183011-3#149#162#diseaseC0018801","span":{"begin":573,"end":586},"obj":"diseaseC0018801"},{"id":"25183011-3#149#162#diseaseC0018802","span":{"begin":573,"end":586},"obj":"diseaseC0018802"},{"id":"25183011-3#226#239#diseaseC0018801","span":{"begin":650,"end":663},"obj":"diseaseC0018801"},{"id":"25183011-3#226#239#diseaseC0018802","span":{"begin":650,"end":663},"obj":"diseaseC0018802"},{"id":"25183011-9#16#23#gene664612","span":{"begin":1371,"end":1378},"obj":"gene664612"},{"id":"25183011-9#16#23#gene664612","span":{"begin":1371,"end":1378},"obj":"gene664612"},{"id":"25183011-9#85#98#diseaseC0018801","span":{"begin":1440,"end":1453},"obj":"diseaseC0018801"},{"id":"25183011-9#85#98#diseaseC0018802","span":{"begin":1440,"end":1453},"obj":"diseaseC0018802"},{"id":"25183011-9#109#127#diseaseC0025517","span":{"begin":1464,"end":1482},"obj":"diseaseC0025517"}],"relations":[{"id":"29#32#gene10724149#162#diseaseC0018801","pred":"associated_with","subj":"25183011-3#29#32#gene10724","obj":"25183011-3#149#162#diseaseC0018801"},{"id":"29#32#gene10724149#162#diseaseC0018802","pred":"associated_with","subj":"25183011-3#29#32#gene10724","obj":"25183011-3#149#162#diseaseC0018802"},{"id":"29#32#gene10724226#239#diseaseC0018801","pred":"associated_with","subj":"25183011-3#29#32#gene10724","obj":"25183011-3#226#239#diseaseC0018801"},{"id":"29#32#gene10724226#239#diseaseC0018802","pred":"associated_with","subj":"25183011-3#29#32#gene10724","obj":"25183011-3#226#239#diseaseC0018802"},{"id":"16#23#gene66461285#98#diseaseC0018801","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#85#98#diseaseC0018801"},{"id":"16#23#gene66461285#98#diseaseC0018802","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#85#98#diseaseC0018802"},{"id":"16#23#gene664612109#127#diseaseC0025517","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#109#127#diseaseC0025517"},{"id":"16#23#gene66461285#98#diseaseC0018801","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#85#98#diseaseC0018801"},{"id":"16#23#gene66461285#98#diseaseC0018802","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#85#98#diseaseC0018802"},{"id":"16#23#gene664612109#127#diseaseC0025517","pred":"associated_with","subj":"25183011-9#16#23#gene664612","obj":"25183011-9#109#127#diseaseC0025517"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-Glycan","denotations":[{"id":"T1","span":{"begin":225,"end":233},"obj":"Glycan"},{"id":"T2","span":{"begin":310,"end":318},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G49108TO"},{"id":"A3","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G49108TO"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G49108TO"},{"id":"A4","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G49108TO"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"Body_part"},{"id":"T2","span":{"begin":169,"end":174},"obj":"Body_part"},{"id":"T3","span":{"begin":483,"end":488},"obj":"Body_part"},{"id":"T4","span":{"begin":573,"end":578},"obj":"Body_part"},{"id":"T5","span":{"begin":650,"end":655},"obj":"Body_part"},{"id":"T6","span":{"begin":1309,"end":1314},"obj":"Body_part"},{"id":"T7","span":{"begin":1440,"end":1445},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A4","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A5","pred":"mat_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A6","pred":"mat_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A7","pred":"mat_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MAT_0000036"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":573,"end":586},"obj":"Phenotype"},{"id":"T2","span":{"begin":650,"end":663},"obj":"Phenotype"},{"id":"T3","span":{"begin":1440,"end":1453},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0001635"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0001635"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0001635"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":573,"end":586},"obj":"Disease"},{"id":"T2","span":{"begin":650,"end":663},"obj":"Disease"},{"id":"T3","span":{"begin":1440,"end":1453},"obj":"Disease"},{"id":"T4","span":{"begin":1458,"end":1482},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005252"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MONDO_0005252"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005252"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MONDO_0019602"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"Glycan-GlyCosmos","denotations":[{"id":"T1","span":{"begin":225,"end":233},"obj":"Glycan"},{"id":"T2","span":{"begin":310,"end":318},"obj":"Glycan"}],"attributes":[{"id":"A1","pred":"glycosmos_id","subj":"T1","obj":"https://glycosmos.org/glycans/show/G49108TO"},{"id":"A3","pred":"image","subj":"T1","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G49108TO"},{"id":"A2","pred":"glycosmos_id","subj":"T2","obj":"https://glycosmos.org/glycans/show/G49108TO"},{"id":"A4","pred":"image","subj":"T2","obj":"https://api.glycosmos.org/wurcs2image/latest/png/binary/G49108TO"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":225,"end":233},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T2","span":{"begin":310,"end":318},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0004"},{"id":"A2","pred":"glycoepitope_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0004"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-HP","denotations":[{"id":"T1","span":{"begin":573,"end":586},"obj":"Phenotype"},{"id":"T2","span":{"begin":650,"end":663},"obj":"Phenotype"},{"id":"T3","span":{"begin":1440,"end":1453},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0001635"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0001635"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0001635"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-CL","denotations":[{"id":"T1","span":{"begin":1044,"end":1058},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000746"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-UBERON","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"Body_part"},{"id":"T5","span":{"begin":169,"end":174},"obj":"Body_part"},{"id":"T9","span":{"begin":402,"end":413},"obj":"Body_part"},{"id":"T10","span":{"begin":483,"end":488},"obj":"Body_part"},{"id":"T14","span":{"begin":573,"end":578},"obj":"Body_part"},{"id":"T18","span":{"begin":650,"end":655},"obj":"Body_part"},{"id":"T22","span":{"begin":1044,"end":1058},"obj":"Body_part"},{"id":"T23","span":{"begin":1309,"end":1314},"obj":"Body_part"},{"id":"T27","span":{"begin":1440,"end":1445},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A3","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A4","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A6","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A7","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A8","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A11","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A12","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A13","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A15","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A16","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A17","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A19","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A20","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A21","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A22","pred":"uberon_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/CL_0000746"},{"id":"A23","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A24","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A25","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A26","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A27","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A28","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A29","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A30","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-MONDO","denotations":[{"id":"T1","span":{"begin":573,"end":586},"obj":"Disease"},{"id":"T2","span":{"begin":650,"end":663},"obj":"Disease"},{"id":"T3","span":{"begin":1440,"end":1453},"obj":"Disease"},{"id":"T4","span":{"begin":1464,"end":1482},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"MONDO:0005252"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"MONDO:0005252"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"MONDO:0005252"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"MONDO:0005066"}],"namespaces":[{"prefix":"MONDO","uri":"http://purl.obolibrary.org/obo/MONDO_"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-Taxon","denotations":[{"id":"T1","span":{"begin":1040,"end":1043},"obj":"Organism"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"10114"},{"id":"A2","pred":"db_id","subj":"T1","obj":"10116"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-GlycoEpitope","denotations":[{"id":"T1","span":{"begin":225,"end":233},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"},{"id":"T2","span":{"begin":310,"end":318},"obj":"http://purl.jp/bio/12/glyco/glycan#Glycan_epitope"}],"attributes":[{"id":"A1","pred":"glycoepitope_id","subj":"T1","obj":"http://www.glycoepitope.jp/epitopes/EP0004"},{"id":"A2","pred":"glycoepitope_id","subj":"T2","obj":"http://www.glycoepitope.jp/epitopes/EP0004"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-Sentences","blocks":[{"id":"T1","span":{"begin":0,"end":85},"obj":"Sentence"},{"id":"T2","span":{"begin":86,"end":175},"obj":"Sentence"},{"id":"T3","span":{"begin":176,"end":423},"obj":"Sentence"},{"id":"T4","span":{"begin":424,"end":679},"obj":"Sentence"},{"id":"T5","span":{"begin":680,"end":783},"obj":"Sentence"},{"id":"T6","span":{"begin":784,"end":856},"obj":"Sentence"},{"id":"T7","span":{"begin":857,"end":1001},"obj":"Sentence"},{"id":"T8","span":{"begin":1002,"end":1237},"obj":"Sentence"},{"id":"T9","span":{"begin":1238,"end":1354},"obj":"Sentence"},{"id":"T10","span":{"begin":1355,"end":1483},"obj":"Sentence"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-FMA","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"Body_part"},{"id":"T2","span":{"begin":169,"end":174},"obj":"Body_part"},{"id":"T3","span":{"begin":402,"end":413},"obj":"Body_part"},{"id":"T4","span":{"begin":483,"end":488},"obj":"Body_part"},{"id":"T5","span":{"begin":573,"end":578},"obj":"Body_part"},{"id":"T6","span":{"begin":650,"end":655},"obj":"Body_part"},{"id":"T7","span":{"begin":1044,"end":1058},"obj":"Body_part"},{"id":"T8","span":{"begin":1309,"end":1314},"obj":"Body_part"},{"id":"T9","span":{"begin":1440,"end":1445},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"FMA:7088"},{"id":"A2","pred":"db_id","subj":"T2","obj":"FMA:7088"},{"id":"A3","pred":"db_id","subj":"T3","obj":"FMA:66835"},{"id":"A4","pred":"db_id","subj":"T4","obj":"FMA:7088"},{"id":"A5","pred":"db_id","subj":"T5","obj":"FMA:7088"},{"id":"A6","pred":"db_id","subj":"T6","obj":"FMA:7088"},{"id":"A7","pred":"db_id","subj":"T7","obj":"FMA:14067"},{"id":"A8","pred":"db_id","subj":"T8","obj":"FMA:7088"},{"id":"A9","pred":"db_id","subj":"T9","obj":"FMA:7088"}],"namespaces":[{"prefix":"FMA","uri":"http://purl.org/sig/ont/fma/fma"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"GlyCosmos15-MAT","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"Body_part"},{"id":"T2","span":{"begin":169,"end":174},"obj":"Body_part"},{"id":"T3","span":{"begin":483,"end":488},"obj":"Body_part"},{"id":"T4","span":{"begin":573,"end":578},"obj":"Body_part"},{"id":"T5","span":{"begin":650,"end":655},"obj":"Body_part"},{"id":"T6","span":{"begin":1309,"end":1314},"obj":"Body_part"},{"id":"T7","span":{"begin":1440,"end":1445},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A2","pred":"mat_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A3","pred":"mat_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A4","pred":"mat_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A5","pred":"mat_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A6","pred":"mat_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MAT_0000036"},{"id":"A7","pred":"mat_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/MAT_0000036"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":1040,"end":1043},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"10114"},{"id":"A2","pred":"db_id","subj":"T1","obj":"10116"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":40,"end":45},"obj":"Body_part"},{"id":"T5","span":{"begin":169,"end":174},"obj":"Body_part"},{"id":"T9","span":{"begin":402,"end":413},"obj":"Body_part"},{"id":"T10","span":{"begin":483,"end":488},"obj":"Body_part"},{"id":"T14","span":{"begin":573,"end":578},"obj":"Body_part"},{"id":"T18","span":{"begin":650,"end":655},"obj":"Body_part"},{"id":"T22","span":{"begin":1044,"end":1058},"obj":"Body_part"},{"id":"T23","span":{"begin":1309,"end":1314},"obj":"Body_part"},{"id":"T27","span":{"begin":1440,"end":1445},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A2","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A3","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A4","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A6","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A7","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A8","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/GO_0005737"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A11","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A12","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A13","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A14","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A15","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A16","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A17","pred":"uberon_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A18","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A19","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A20","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A21","pred":"uberon_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A22","pred":"uberon_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/CL_0000746"},{"id":"A23","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A24","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A25","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A26","pred":"uberon_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"},{"id":"A27","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A28","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0007100"},{"id":"A29","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0015228"},{"id":"A30","pred":"uberon_id","subj":"T27","obj":"http://purl.obolibrary.org/obo/UBERON_0015230"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}

{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":1044,"end":1058},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000746"}],"text":"MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression.\nDerangements in metabolism and related signaling pathways characterize the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), is an essential post-translational modification regulated by two enzymes, O-GlcNAc transferase and O-GlcNAcase (OGA), which modulate the function of many nuclear and cytoplasmic proteins. We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, molecular mechanisms regulating these enzymes during heart failure remain unknown. Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. Here, we focused on miR-539 because it was predicted to target OGA mRNA. Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. Overexpression of miR-539 in neonatal rat cardiomyocytes significantly suppressed OGA expression and consequently increased O-GlcNAcylation; conversely, the miR-539 inhibitor rescued OGA protein expression and restored O-GlcNAcylation. In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases."}