کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5525748 1546685 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers
چکیده انگلیسی


- A new role for miR-939 in breast cancer is proposed.
- miR-939 interaction with lymph node status predicts worse prognosis in TNBCs.
- miR-939 is released in exosomes and regulates VE-cadherin in endothelial cells.
- Down modulation of VE-cadherin enhances cancer cells trans-endothelial migration.

Exosomes-secreted microRNAs play an important role in metastatic spread. During this process breast cancer cells acquire the ability to transmigrate through blood vessels by inducing changes in the endothelial barrier. We focused on miR-939 that is predicted to target VE-cadherin, a component of adherens junction involved in vessel permeability. By in silico analysis miR-939 was found highly expressed in the basal-like tumor subtypes and in our cohort of 63 triple-negative breast cancers (TNBCs) its expression significantly interacted with lymph node status in predicting disease-free survival probability. We demonstrated, in vitro, that miR-939 directly targets VE-cadherin leading to an increase in HUVECs monolayer permeability. MDA-MB-231 cells transfected with a miR-939 mimic, released miR-939 in exosomes that, once internalized in endothelial cells, favored trans-endothelial migration of MDA-MB-231-GFP cells by the disruption of the endothelial barrier. Notably, when up taken in endothelial cells exosomes caused VE-cadherin down-regulation specifically through miR-939 as we demonstrated by inhibiting miR-939 expression in exosomes-releasing TNBC cells.Together, our data indentify an extracellular pro-tumorigenic role for tumor-derived, exosome-associated miR-939 that can explain its association with worse prognosis in TNBCs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 384, 1 January 2017, Pages 94-100
نویسندگان
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