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

フォーマット:

論文

責任表示:

Oda, Yuki ; Nakajima, Miki ; Mohri, Takuya ; Takamiya, Masataka ; Aoki, Yasuhiro ; Fukami, Tatsuki ; Yokoi, Tsuyoshi

言語:

英語

出版情報:

Elsevier, 2012-05-01

著者名:

Oda, Yuki

Nakajima, Miki

Mohri, Takuya

Takamiya, Masataka

Aoki, Yasuhiro

Fukami, Tatsuki

Yokoi, Tsuyoshi

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掲載情報:

Toxicology and Applied Pharmacology

ISSN:

0041-008x      

巻:

260

通号:

3

開始ページ:

222

終了ページ:

231

バージョン:

author

概要:

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. © 2012 Elsevier Inc. 続きを見る

URL:

http://hdl.handle.net/2297/31390