| RRC ID |
43709
|
| 著者 |
Oda Y, Nakajima M, Mohri T, Takamiya M, Aoki Y, Fukami T, Yokoi T.
|
| タイトル |
Aryl hydrocarbon receptor nuclear translocator in human liver is regulated by miR-24.
|
| ジャーナル |
Toxicol Appl Pharmacol
|
| 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.
|
| 巻・号 |
260(3)
|
| ページ |
222-31
|
| 公開日 |
2012-5-1
|
| DOI |
10.1016/j.taap.2012.02.012
|
| PII |
S0041-008X(12)00067-1
|
| PMID |
22387692
|
| MeSH |
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*
|
| IF |
3.347
|
| 引用数 |
28
|
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
TOXICOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7
Hep G2 |
