| Literature DB >> 28991221 |
David Gilot1, Mélodie Migault1, Laura Bachelot1, Fabrice Journé2, Aljosja Rogiers3,4, Emmanuelle Donnou-Fournet1, Ariane Mogha1, Nicolas Mouchet1, Marie-Laure Pinel-Marie5, Bernard Mari6, Tristan Montier7,8, Sébastien Corre1, Arthur Gautron1, Florian Rambow3,4, Petra El Hajj2, Rania Ben Jouira9, Sophie Tartare-Deckert9, Jean-Christophe Marine3,4, Brice Felden5, Ghanem Ghanem2, Marie-Dominique Galibert1,10.
Abstract
Competition among RNAs to bind miRNA is proposed to influence biological systems. However, the role of this competition in disease onset is unclear. Here, we report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly promotes cell proliferation by sequestering miR-16 on non-canonical miRNA response elements. Consequently, the sequestered miR-16 is no longer able to repress its mRNA targets, such as RAB17, which is involved in melanoma cell proliferation and tumour growth. Restoration of miR-16 tumour-suppressor function can be achieved in vitro by silencing TYRP1 or increasing miR-16 expression. Importantly, TYRP1-dependent miR-16 sequestration can also be overcome in vivo by using small oligonucleotides that mask miR-16-binding sites on TYRP1 mRNA. Together, our findings assign a pathogenic non-coding function to TYRP1 mRNA and highlight miRNA displacement as a promising targeted therapeutic approach for melanoma.Entities:
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Year: 2017 PMID： 28991221 DOI： 10.1038/ncb3623
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824