OPN3 Regulates Melanogenesis in Human Congenital Melanocytic Nevus Cells through Functional Interaction with...

OPN3, as a member of the opsin family, has various nonlight-dependent functions. Congenital melanocytic nevus (CMN) is a skin lesion with dark pigmentation that appears at birth and can be initiated by the BRAF^V600E mutation in melanocytes. However, the role of OPN3 in BRAF^V600E CMN cell melanogenesis has never been reported. In this study, we show that OPN3 acts as a negative regulator of melanin production by modulating BRAF^V600E signaling in BRAF^V600E CMN cells. Knocking down OPN3 expression can inhibit the BRAF^V600E/extracellular signal‒regulated kinase signaling pathway and upregulate the expression of microcephaly-related transcription factors, tyrosinase, and TRP1 and TRP2, thus increasing melanin levels in BRAF^V600E CMN cells. More remarkably, OPN3 and BRAF^V600E were found to form a physical complex. Furthermore, a three-dimensional nevus model was used to further prove the negative regulatory effect of OPN3 on BRAF^V600E CMN cell melanogenesis. Our study reveals a mechanism for OPN3-mediated melanogenesis in BRAF^V600E CMN cells, and these results may lead to a more personalized and economically viable approach to treating BRAF^V600E CMN.