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A noncoding function of TYRP1 mRNA promotes melanoma growth

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 governs cell proliferation by sequestering miR-16 to non-canonical miRNA response elements (MREs). 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 tumor growth. Restoration of miR-16 tumor 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 the TYRP1 mRNA. Together, our findings assign a pathogenic noncoding function to the TYRP1 mRNA and highlight miRNA displacement as a new targeted therapeutic approach in melanoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95589 | GEO | 2017/08/08

SECONDARY ACCESSION(S): PRJNA377570

REPOSITORIES: GEO

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