MicroRNA-5110 regulates pigmentation by cotargeting melanophilin and WNT family member 1.

Mammalian pigmentation requires the production of melanin by melanocytes and its transfer to neighboring keratinocytes. These complex processes are regulated by several molecular pathways. Melanophilin ( MLPH) and WNT family member 1 ( WNT1), known to be involved in melanin transfer and melanin production, respectively, were predicted to be targets of microRNA-5110 using bioinformatics. In the current study, we investigated the effects of microRNA-5110 on pigmentation in alpaca ( Vicugna pacos) melanocytes. In situ hybridization identified high levels of microRNA-5110 in the cytoplasm of alpaca melanocytes. Luciferase activity assays confirmed that MLPH and WNT1 were targeted by microRNA-5110 in these cells. Overexpression and knockdown of microRNA-5110 in alpaca melanocytes downregulated and upregulated MLPH and WNT1 expression at the mRNA and protein levels, respectively. In addition, overexpression and knockdown of microRNA-5110 in alpaca melanocytes decreased and increased, respectively, the mRNA levels of the melanin transfer-related genes, rat sarcoma (RAS)-associated binding ( RAB27a) and myosin 5a ( MYO5a); the mRNA levels of microphthalmia-associated transcription factor ( MITF), tyrosinase ( TYR), and tyrosinase-related protein ( TYRP) 1; and the production of total alkali melanin and pheomelanin. In contrast, overexpression and knockdown of microRNA-5110 increased and decreased the mRNA levels of TYRP2, respectively. Overexpression of microRNA-5110 also increased eumelanin. These results indicate that microRNA-5110 regulates pigmentation in alpaca melanocytes by directly targeting MLPH and WNT1 to affect eumelanin production and transfer.-Yang, S., Liu, B., Ji, K., Fan, R., Dong, C. MicroRNA-5110 regulates pigmentation by cotargeting melanophilin and WNT family member 1.