Regulation of MicroRNA 183 by Cyclooxygenase 2 in Liver Is DEAD-Box Helicase p68 (DDX5) Dependent: Role in Insulin Signaling.
Cyclooxygenase (COX) catalyzes the first step in prostanoid biosynthesis and exists as two isoforms. COX-1 is a constitutive enzyme involved in physiological processes, whereas COX-2 is induced by a variety of stimuli. MicroRNAs (miRNAs) are noncoding RNAs that function as key posttranscriptional regulators of gene expression. Although it is known ... that COX-2 expression is regulated by miRNAs, there are no data regarding COX-2 involvement in miRNA regulation. Considering our previous results showing that COX-2 expression in hepatocytes protects against insulin resistance, we evaluated the role of COX-2 in the regulation of a specific set of miRNAs implicated in insulin signaling in liver cells. Our results provide evidence of the molecular basis for a novel function of COX-2 in miRNA processing. COX-2 represses miRNA 23b (miR-23b), miR-146b, and miR-183 expression in liver cells by increasing the level of DEAD-box helicase p68 (DDX5) through phosphatidylinositol 3-kinase (PI3K)/p300 signaling and by modulating the enzymatic function of the Drosha (RNase type III) complex through its physical association with DDX5. The decrease of miR-183 expression promotes protection against insulin resistance by increasing insulin receptor substrate 1 (IRS1) levels. These results indicate that the modulation of miRNA processing by COX-2 is a key event in insulin signaling in liver and has potential clinical implications for the management of various hepatic dysfunctions.
Mesh Terms:
Animals, Blotting, Western, Cell Line, Cell Line, Tumor, Cyclooxygenase 2, DEAD-box RNA Helicases, Gene Expression Regulation, Hepatocytes, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Liver, Mice, Transgenic, MicroRNAs, Phosphatidylinositol 3-Kinases, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III
Animals, Blotting, Western, Cell Line, Cell Line, Tumor, Cyclooxygenase 2, DEAD-box RNA Helicases, Gene Expression Regulation, Hepatocytes, Humans, Insulin Receptor Substrate Proteins, Insulin Resistance, Liver, Mice, Transgenic, MicroRNAs, Phosphatidylinositol 3-Kinases, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Ribonuclease III
Mol. Cell. Biol.
Date: Jul. 01, 2015
PubMed ID: 25963660
View in: Pubmed Google Scholar
Download Curated Data For This Publication
199627
Switch View:
- Interactions 2