کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815391 | 1058471 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis
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کلمات کلیدی
NF-κBPBMCIPZIKKNLSsPMCSNESS3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide - 3- [4،5-dimethylthiazol-2-yl] -2،5-diphenyltetrazolium bromideIκB kinase - IkB kinaseMTT - MTTNPCs - NPC هاSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAtumour necrosis factor-α - تومور نکروز عامل αNuclear export signals - سیگنال های صادرات هسته ایTNF-α - فاکتور نکروز توموری آلفاnuclear factor-κB - فاکتور هسته ای κBMultiple myeloma - مولتیپل میلوماPropidium iodide - پروتئین یدیدnegative control - کنترل منفی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis](/preview/png/10815391.png)
چکیده انگلیسی
Multiple myeloma (MM) is a plasma cell neoplasm that is currently incurable. The activation of nuclear factor-κB (NF-κB) signalling plays a crucial role in the immortalisation of MM cells. As the most important transcription factor of the canonical NF-κB pathway, the p50/p65 heterodimer requires transportation into the nucleus for its successful signal transduction. Importin β1 is the key transport receptor that mediates p50/p65 nuclear import. Currently, it remains unclear whether the regulation of importin β1 function affects the biological behaviour of MM cells. In the present study, we investigated the changes in p65 translocation and the proliferation and apoptosis of MM cells after treatment with small interfering RNA (siRNA) or an importin β1 inhibitor. The underlying mechanisms were also investigated. We found importin β1 over-expression and the excessive nuclear transport of p65 in myeloma cells. Confocal laser scanning microscopy and Western blot analysis results indicated that p65 nuclear transport was blocked after inhibiting importin β1 expression with siRNA and the importin β1-specific inhibitor importazole (IPZ). Importantly, electronic mobility shift assay results also verified that p65 nuclear transport was dramatically reduced. Moreover, the expression of the NF-κB signalling target genes involved in MM cell apoptosis, such as BCL-2, c-IAP1 and XIAP, were markedly reduced, as demonstrated by the RT-PCR results. Furthermore, the proliferation of MM cells was inhibited, as demonstrated by MTT assay results, and the MM cell apoptosis rate was higher, as demonstrated by the annexin V/propidium iodide (PI) double-staining assay results. Additionally, the percentage of S phase cells in the myeloma cell lines treated with IPZ was dramatically reduced. In conclusion, our results clearly show that importin β1 mediates the translocation of NF-κB into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis, which provides new insights for targeted myeloma therapies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 4, April 2015, Pages 851-859
Journal: Cellular Signalling - Volume 27, Issue 4, April 2015, Pages 851-859
نویسندگان
Wenqing Yan, Rong Li, Jie He, Juan Du, Jian Hou,