Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24.

Abstract

Aryl hydrocarbon receptor nuclear translocator (ARNT) forms a heterodimer with aryl hydrocarbon receptor or hypoxia inducible factor 1α to mediate biological responses to xenobiotic exposure and hypoxia. Although the regulation mechanism of the ARNT expression is largely unknown, earlier studies reported that the human ARNT protein level was decreased by hydrogen peroxide or reactive oxygen species. These stimuli increase the miR-24 level in various human cell lines. In silico analysis predicts that some microRNAs including miR-16 and miR-23b may bind to ARNT mRNA. This background prompted us to investigate whether human ARNT is regulated by microRNAs. Overexpression of miR-24 into HuH-7 and HepG2 cells significantly decreased the ARNT protein level, but not the ARNT mRNA level, indicating translational repression. However, overexpression of miR-16 or miR-23b caused no change in the ARNT expression. The miR-24-dependent down-regulation of ARNT decreased the expression of its downstream genes such as CYP1A1 and carbonic anhydrase IX. Luciferase assay was performed to determine the element on the ARNT mRNA to which miR-24 binds. Finally, it was demonstrated that the miR-24 levels in a panel of 26 human livers were inversely correlated with the protein levels or the translational efficiency of ARNT. Taken together, we found that miR-24 negatively regulates ARNT expression in human liver, affecting the expression of its downstream genes. miR-24 would be one of the factors underlying the mechanisms by which ARNT protein is decreased by reactive oxygen species.

• Authors: Yuki Oda, Miki Nakajima, Takuya Mohri, Masataka Takamiya, Yasuhiro Aoki, Tatsuki Fukami, Tsuyoshi Yokoi
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 260 Issue 3 Pg. 222-31 (May 01 2012) ISSN: 1096-0333 [Electronic] United States
• PMID: 22387692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• MIRN16 microRNA, human
• MIRN23a microRNA, human
• MIRN24 microRNA, human
• MicroRNAs
• Reactive Oxygen Species
• Aryl Hydrocarbon Receptor Nuclear Translocator
• Hydrogen Peroxide

Topics

• Aryl Hydrocarbon Receptor Nuclear Translocator (genetics)
• Carcinoma, Hepatocellular (genetics)
• Cell Line, Tumor
• Down-Regulation (genetics)
• Hep G2 Cells
• Humans
• Hydrogen Peroxide (metabolism)
• Liver (metabolism)
• Liver Neoplasms (genetics)
• MicroRNAs (genetics)
• Reactive Oxygen Species (metabolism)