دورية أكاديمية
Oncosuppressive miRNAs loaded in lipid nanoparticles potentiate targeted therapies in BRAF-mutant melanoma by inhibiting core escape pathways of resistance
| العنوان: | Oncosuppressive miRNAs loaded in lipid nanoparticles potentiate targeted therapies in BRAF-mutant melanoma by inhibiting core escape pathways of resistance |
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| المؤلفون: | Fattore, Luigi, Cafaro, Giordana, Di Martile, Marta, Campani, Virginia, Sacconi, Andrea, Liguoro, Domenico, Marra, Emanuele, Bruschini, Sara, Stoppoloni, Daniela, Cirombella, Roberto, De Nicola, Francesca, Pallocca, Matteo, Ruggiero, Ciro F., Castaldo, Vittorio, Catizone, Angiolina, Del Bufalo, Donatella, Viglietto, Giuseppe, Vecchione, Andrea, Blandino, Giovanni, Aurisicchio, Luigi, Fanciulli, Maurizio, Ascierto, Paolo A., De Rosa, Giuseppe, Mancini, Rita, Ciliberto, Gennaro |
| المصدر: | Oncogene ; volume 42, issue 4, page 293-307 ; ISSN 0950-9232 1476-5594 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Genetics, Molecular Biology |
| الوصف: | BRAF-mutated melanoma relapsing after targeted therapies is an aggressive disease with unmet clinical need. Hence the need to identify novel combination therapies able to overcome drug resistance. miRNAs have emerged as orchestrators of non-genetic mechanisms adopted by melanoma cells to challenge therapies. In this context we previously identified a subset of oncosuppressor miRNAs downregulated in drug-resistant melanomas. Here we demonstrate that lipid nanoparticles co-encapsulating two of them, miR-199-5p and miR-204-5p, inhibit tumor growth both in vitro and in vivo in combination with target therapy and block the development of drug resistance. Mechanistically they act by directly reducing melanoma cell growth and also indirectly by hampering the recruitment and reprogramming of pro-tumoral macrophages. Molecularly, we demonstrate that the effects on macrophages are mediated by the dysregulation of a newly identified miR-204-5p-miR-199b-5p/CCL5 axis. Finally, we unveiled that M2 macrophages programs are molecular signatures of resistance and predict response to therapy in patients. Overall, these findings have strong translational implications to propose new combination therapies making use of RNA therapeutics for metastatic melanoma patients. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41388-022-02547-9 |
| الإتاحة: | https://doi.org/10.1038/s41388-022-02547-9Test https://www.nature.com/articles/s41388-022-02547-9.pdfTest https://www.nature.com/articles/s41388-022-02547-9Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.98C4EE30 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-022-02547-9 |
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