論文 - 詳細
| RRC ID | 66100 |
|---|---|
| 著者 | Carabia J, Carpio C, Abrisqueta P, Jiménez I, Purroy N, Calpe E, Palacio C, Bosch F, Crespo M. |
| タイトル | Microenvironment regulates the expression of miR-21 and tumor suppressor genes PTEN, PIAS3 and PDCD4 through ZAP-70 in chronic lymphocytic leukemia. |
| ジャーナル | Sci Rep |
| Abstract |
Chronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironment, being the BCR pathway one key player in this crosstalk. Among proteins participating, ZAP-70 enhances response to microenvironmental stimuli. MicroRNA-21 (miR-21) is overexpressed in diverse neoplasias including CLL, where it has been associated to refractoriness to fludarabine and to shorter time to progression and survival. To further elucidate the role of ZAP-70 in the biology of CLL, we studied its involvement in miR-21 regulation. MiR-21 expression was higher in CLL cells with high ZAP-70. Ectopic expression of ZAP-70 induced transcription of miR-21 via MAPK and STAT3, which subsequently induced downregulation of tumor suppressors targeted by miR-21. The co-culture of primary CLL cells mimicking the microenvironment induced ZAP-70 and miR-21 expression, as well as downregulation of miR-21 targets. Interestingly, the increase in miR-21 after co-culture was significantly impaired by ibrutinib, indicating that the BCR signaling pathway is involved in its regulation. Finally, survival of CLL cells induced by the co-culture correlated with miR-21 upregulation. In conclusion, stimuli from the microenvironment regulate miR-21 and its targeted tumor suppressor genes via a signaling pathway involving ZAP-70, thus contributing to the cytoprotection offered by the microenvironment particularly observed in CLL cells expressing ZAP-70. |
| 巻・号 | 7(1) |
| ページ | 12262 |
| 公開日 | 2017-9-25 |
| DOI | 10.1038/s41598-017-12135-7 |
| PII | 10.1038/s41598-017-12135-7 |
| PMID | 28947822 |
| PMC | PMC5612928 |
| MeSH | Apoptosis Regulatory Proteins / biosynthesis* Cells, Cultured Coculture Techniques Gene Expression Regulation* Gene Regulatory Networks Humans Leukemia, Lymphocytic, Chronic, B-Cell / pathology* Leukocytes, Mononuclear / chemistry MicroRNAs / biosynthesis* Molecular Chaperones / biosynthesis* PTEN Phosphohydrolase / biosynthesis* Protein Inhibitors of Activated STAT / biosynthesis* RNA-Binding Proteins / biosynthesis* Signal Transduction Tumor Microenvironment ZAP-70 Protein-Tyrosine Kinase / biosynthesis* |
| IF | 3.998 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 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 | UE6E7T-2(RCB2153) |