論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Rat-1(RCB1830) |