論文 - 詳細
| RRC ID | 18111 |
|---|---|
| 著者 | Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, Mano H, Sugimoto K, Miyazono K. |
| タイトル | miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. |
| ジャーナル | Blood |
| Abstract |
Many transformed lymphoma cells show immune-phenotypes resembling the corresponding normal lymphocytes; thus, they provide a guide for proper diagnosis and present promising routes to improve their pathophysiologic understanding and to identify novel therapeutic targets. However, the underlying molecular mechanism(s) of these aberrant immune-phenotypes is largely unknown. Here, we report that microRNA-135b (miR-135b) mediates nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-driven oncogenicity and empowers IL-17-producing immunophenotype in anaplastic large cell lymphoma (ALCL). NPM-ALK oncogene strongly promoted the expression of miR-135b and its host gene LEMD1 through activation of signal transducer and activator of transcription (STAT) 3. In turn, elevated miR-135b targeted FOXO1 in ALCL cells. miR-135b introduction also decreased chemosensitivity in Jurkat cells, suggesting its contribution to oncogenic activities of NPM-ALK. Interestingly, miR-135b suppressed T-helper (Th) 2 master regulators STAT6 and GATA3, and miR-135b blockade attenuated IL-17 production and paracrine inflammatory response by ALCL cells, indicating that miR-135b-mediated Th2 suppression may lead to the skewing to ALCL immunophenotype overlapping with Th17 cells. Furthermore, antisense-based miR-135b inhibition reduced tumor angiogenesis and growth in vivo, demonstrating significance of this "Th17 mimic" pathway as a therapeutic target. These results collectively illuminated unique contribution of oncogenic kinase-linked microRNA to tumorigenesis through modulation of tumor immune-phenotype and microenvironment. |
| 巻・号 | 118(26) |
| ページ | 6881-92 |
| 公開日 | 2011-12-22 |
| DOI | 10.1182/blood-2011-05-354654 |
| PII | S0006-4971(20)40244-7 |
| PMID | 22042699 |
| MeSH | 3' Untranslated Regions / genetics Animals Cell Line, Tumor Cell Transformation, Neoplastic / genetics* Cell Transformation, Neoplastic / immunology Cell Transformation, Neoplastic / metabolism Female GATA3 Transcription Factor / genetics GATA3 Transcription Factor / metabolism Gene Expression Regulation, Neoplastic HCT116 Cells HeLa Cells Humans Immunoblotting Immunophenotyping Interleukin-17 / immunology Interleukin-17 / metabolism* Jurkat Cells Lymphoma, Large-Cell, Anaplastic / genetics* Lymphoma, Large-Cell, Anaplastic / pathology Lymphoma, Large-Cell, Anaplastic / prevention & control Mice Mice, SCID MicroRNAs / genetics* MicroRNAs / metabolism Neoplasm Proteins / genetics Neoplasm Proteins / metabolism Oligonucleotides, Antisense / administration & dosage Oligonucleotides, Antisense / genetics Protein-Tyrosine Kinases / genetics* Protein-Tyrosine Kinases / metabolism Reverse Transcriptase Polymerase Chain Reaction STAT3 Transcription Factor / genetics* STAT3 Transcription Factor / metabolism Th17 Cells / immunology Th17 Cells / metabolism Xenograft Model Antitumor Assays |
| IF | 17.794 |
| 引用数 | 114 |
| 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
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | WI-38(RCB0702) |