| RRC ID |
42763
|
| 著者 |
Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T.
|
| タイトル |
MicroRNA regulates the expression of human cytochrome P450 1B1.
|
| ジャーナル |
Cancer Res
|
| Abstract |
MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression through translational repression or mRNA cleavage. Here, we found that cytochrome P450 (CYP), a superfamily of drug-metabolizing enzymes, is a target of miRNA. Human CYP1B1, which is highly expressed in estrogen target tissues, catalyzes the metabolic activation of various procarcinogens and the 4-hydroxylation of 17beta-estradiol. CYP1B1 protein is abundant in cancerous tissues. We identified a near-perfect matching sequence with miR-27b in the 3'-untranslated region of human CYP1B1. Luciferase assays revealed that the reporter activity of the plasmid containing the miR-27b recognition element was decreased in MCF-7 cells (miR-27 positive) but not in Jurkat cells (miR-27b negative). Exogenously expressed miR-27b could decrease the luciferase activity in Jurkat cells. In MCF-7 cells, the antisense oligoribonucleotide for miR-27b restored the luciferase activity and increased the protein level and enzymatic activity of endogenous CYP1B1. These results suggested that human CYP1B1 is post-transcriptionally regulated by miR-27b. The expression levels of miR-27b and CYP1B1 protein in breast cancerous and adjacent noncancerous tissues from 24 patients were evaluated. In most patients, the expression level of miR-27b was decreased in cancerous tissues, accompanied by a high level of CYP1B1 protein. A significant inverse association was observed between the expression levels of miR-27b and CYP1B1 protein. Thus, the decreased expression of miR-27b would be one of causes of the high expression of CYP1B1 protein in cancerous tissues. This is the first study to show that miRNAs regulate not only essential genes for physiologic events but also drug-metabolizing enzymes.
|
| 巻・号 |
66(18)
|
| ページ |
9090-8
|
| 公開日 |
2006-9-15
|
| DOI |
10.1158/0008-5472.CAN-06-1403
|
| PII |
66/18/9090
|
| PMID |
16982751
|
| MeSH |
3' Untranslated Regions
Adult
Aged
Aryl Hydrocarbon Hydroxylases / biosynthesis*
Aryl Hydrocarbon Hydroxylases / genetics
Base Sequence
Breast Neoplasms / enzymology
Breast Neoplasms / genetics
Cell Line, Tumor
Cytochrome P-450 CYP1B1
Female
HeLa Cells
Humans
Jurkat Cells
Luciferases / biosynthesis
Luciferases / genetics
MicroRNAs / genetics*
Middle Aged
Molecular Sequence Data
Oligonucleotides, Antisense / genetics
RNA Processing, Post-Transcriptional
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
|
| IF |
9.727
|
| 引用数 |
288
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
