論文 - 詳細
| RRC ID | 62753 |
|---|---|
| 著者 | Shikama Y, Cao M, Ono T, Feng X, Noji H, Kimura H, Ogawa K, Suzuki Y, Ikeda K, Takeishi Y, Kimura J. |
| タイトル | Reduction of c-Fos via Overexpression of miR-34a Results in Enhancement of TNF- Production by LPS in Neutrophils from Myelodysplastic Syndrome Patients. |
| ジャーナル | PLoS One |
| Abstract |
Although increased TNF-α has been considered to cause ineffective hematopoiesis in myelodysplastic syndromes (MDS), the mechanisms of TNF-α elevation are not known. We recently found that c-Fos mRNA stabilization under translation-inhibiting stimuli was impaired in MDS-derived neutrophilic granulocytes. In the current study, we identified overexpression of c-Fos-targeting miR-34a and miR-155 as the cause of impairment. Expression levels of miR-34a but not miR-155 inversely correlated with ratios of c-Fos-positive cells in MDS-derived CD16+ neutrophils (r = -0.618, P<0.05), which were analyzed by flow cytometry. Among the seventeen patients, c-Fos was detectable in less than 60% of CD16+ cells in eight patients (Group A), while five (Group B) expressed c-Fos in more than 80% of CD16+ cells, which was consistent with the controls (88.6 ± 7.8%). Group A-derived granulocytes secreted more TNF-α in response to 1 μM LPS for 3 hours (735.4 ± 237.5 pg/mL) than Group B (143.5 ± 65.7 pg/mL, P<0.05) and healthy controls (150.8 ± 91.5 pg/mL, P<0.05). Knockdown of c-Fos in neutrophil-like differentiated HL60 increased the binding of NF-κB p65 to the promoter region of TNF-α DNA. Thus, c-Fos reduction via overexpression of miR-34a contributes to TNF-α overproduction under inflammatory stimuli in MDS. |
| 巻・号 | 11(8) |
| ページ | e0158527 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0158527 |
| PII | PONE-D-16-00242 |
| PMID | 27513856 |
| PMC | PMC4981319 |
| MeSH | Aged Aged, 80 and over Case-Control Studies Cell Differentiation / drug effects Female Gene Expression Regulation / drug effects* Granulocytes / drug effects Granulocytes / metabolism Granulocytes / pathology Humans Lipopolysaccharides / pharmacology* Male MicroRNAs / genetics* Middle Aged Myelodysplastic Syndromes / genetics Myelodysplastic Syndromes / immunology Myelodysplastic Syndromes / metabolism* NF-kappa B / genetics NF-kappa B / metabolism Neutrophils / drug effects Neutrophils / metabolism Neutrophils / pathology Proto-Oncogene Proteins c-fos / antagonists & inhibitors* Proto-Oncogene Proteins c-fos / genetics Proto-Oncogene Proteins c-fos / metabolism Signal Transduction / drug effects Tumor Necrosis Factor-alpha / metabolism* |
| IF | 2.74 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | HL60(RCB0041) |