| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-85 |
Sentence |
denotes |
MicroRNA-539 is up-regulated in failing heart, and suppresses O-GlcNAcase expression. |
| T2 |
86-175 |
Sentence |
denotes |
Derangements in metabolism and related signaling pathways characterize the failing heart. |
| T3 |
176-423 |
Sentence |
denotes |
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. |
| T4 |
424-679 |
Sentence |
denotes |
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. |
| T5 |
680-783 |
Sentence |
denotes |
Using miRNA microarray analysis, we observed acute and chronic changes in expression of several miRNAs. |
| T6 |
784-856 |
Sentence |
denotes |
Here, we focused on miR-539 because it was predicted to target OGA mRNA. |
| T7 |
857-1001 |
Sentence |
denotes |
Indeed, co-transfection of the OGA-3'UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced reporter activity. |
| T8 |
1002-1237 |
Sentence |
denotes |
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. |
| T9 |
1238-1354 |
Sentence |
denotes |
In conclusion, this work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. |
| T10 |
1355-1483 |
Sentence |
denotes |
Manipulation of miR-539 may represent a novel therapeutic target in the treatment of heart failure and other metabolic diseases. |
