دورية أكاديمية
Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma
العنوان: | Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma |
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المؤلفون: | Sibbesen, Nina A., Kopp, Katharina L., Litvinov, Ivan V., Willerslev-Olsen, Andreas, Fredholm, Simon, Petersen, David L., Nastasi, Claudia, Lindahl, Lise M., Gniadecki, Robert, Mongan, Nigel P., Sasseville, Denis, Wasik, Mariusz A., Iversen, Lars, Bonefeld, Charlotte M., Geisler, Carsten, Woetmann, Anders, Odum, Niels |
بيانات النشر: | Impact Journals |
سنة النشر: | 2015 |
المجموعة: | University of Nottingham: Repository@Nottingham |
الوصف: | Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | unknown |
العلاقة: | https://nottingham-repository.worktribe.com/output/758595Test; Oncotarget; Volume 6; Issue 24; https://nottingham-repository.worktribe.com/file/758595/1/2015_Oncotarget.pdfTest |
الإتاحة: | https://nottingham-repository.worktribe.com/file/758595/1/2015_Oncotarget.pdfTest https://nottingham-repository.worktribe.com/output/758595Test |
حقوق: | openAccess |
رقم الانضمام: | edsbas.D8780C7E |
قاعدة البيانات: | BASE |
الوصف غير متاح. |