| RRC ID |
37623
|
| 著者 |
Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo YM, Iwamoto K, Yamashita J, Saitoh H, Kameoka Y, Shimizu N, Ichinohasama R, Sawada K.
|
| タイトル |
Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia.
|
| ジャーナル |
Blood
|
| Abstract |
The gene(s) responsible for natural killer (NK)-cell lymphoma/leukemia have not been identified. In the present study, we found that in NK-cell lymphoma lines (n = 10) and specimens of primary lymphoma (n = 10), levels of miR-21 and miR-155 expression were inversely related and were significantly greater than those found in normal natural killer (CD3(-)CD56(+)) cells (n = 8). To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) targeting miR-21 (ASO-21) and/or miR-155 (ASO-155) in NK-cell lymphoma lines overexpressing one or both of these miRNAs. Conversely, cells showing little endogenous expression of miR-21 or miR-155 were transduced by the use of lentiviral vectors, leading to their overexpression. Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). ASO-21- and ASO-155-treated cell lines all showed down-regulation of phosphorylated AKT(ser473). Moreover, transduction with either miR-21 or miR-155 led to down-regulation of PTEN and PDCD4 or SHIP1 with up-regulation of phosphorylated AKT(ser473). Collectively, these results provide important new insight into the pathogenesis of NK-cell lymphoma/leukemia and suggest targeting miR-21 and/or miR-155 may represent a useful approach to treating NK-cell lymphoma/leukemia.
|
| 巻・号 |
114(15)
|
| ページ |
3265-75
|
| 公開日 |
2009-10-8
|
| DOI |
10.1182/blood-2009-06-222794
|
| PII |
S0006-4971(20)36802-6
|
| PMID |
19641183
|
| MeSH |
Adult
Aged
Aged, 80 and over
Apoptosis Regulatory Proteins / biosynthesis
Apoptosis Regulatory Proteins / genetics
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic*
Humans
Inositol Polyphosphate 5-Phosphatases
Killer Cells, Natural*
Lentivirus
Lymphoma / genetics
Lymphoma / metabolism*
Lymphoma / pathology
Male
MicroRNAs / antagonists & inhibitors
MicroRNAs / biosynthesis*
MicroRNAs / genetics
Middle Aged
Oligodeoxyribonucleotides, Antisense
PTEN Phosphohydrolase / biosynthesis
PTEN Phosphohydrolase / genetics
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Phosphoric Monoester Hydrolases / biosynthesis
Phosphoric Monoester Hydrolases / genetics
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
RNA, Neoplasm / antagonists & inhibitors
RNA, Neoplasm / biosynthesis*
RNA, Neoplasm / genetics
RNA-Binding Proteins / biosynthesis
RNA-Binding Proteins / genetics
Signal Transduction*
Transduction, Genetic
|
| IF |
17.794
|
| 引用数 |
149
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
Rat-1(RCB1830) |
