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.

中文翻译：

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TYRP1 mRNA的非编码功能促进黑色素瘤的生长。

RNA之间结合miRNA的竞争被提议影响生物系统。但是，这种竞争在疾病发作中的作用尚不清楚。在这里，我们报告TYRP1 mRNA，除了编码酪氨酸酶相关蛋白1（TYRP1）外，通过在非规范miRNA反应元件上隔离miR-16间接促进细胞增殖。因此，隔离的miR-16不再能够抑制它的mRNA靶标，例如RAB17，它参与了黑色素瘤细胞的增殖和肿瘤的生长。通过沉默TYRP1或增加miR-16的表达，可以在体外实现miR-16肿瘤抑制功能的恢复。重要的是，还可以通过使用掩盖TYRP1 mRNA上miR-16结合位点的小的寡核苷酸在体内克服TYRP1依赖的miR-16隔离问题。一起，